72,166 results on '"Chemistry, Pharmaceutical"'
Search Results
2. Leo Sternbach and the benzodiazepines 60 years on: A revolutionary treatment for anxiety disorders.
- Author
-
Junkes, Larissa, Mendlowicz, Mauro V., Shader, Richard, and Nardi, Antonio E.
- Subjects
- *
HISTORY of medicine , *ANXIETY disorders , *PSYCHOPHARMACOLOGY , *BENZODIAZEPINES , *PHARMACOLOGY - Abstract
[Display omitted] • Until the 1960s, the treatment of anxiety disorders was quite limited. • Leo Sternbach was the chemist who first synthesized a benzodiazepine. • Benzodiazepines helped in identifying pharmacological targets for treating anxiety. • The current goal is to create specific agonists for the GABA-A receptor α2-subtype. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Differences in fluidity and viscosity of brand-name and generic injectable ointment.
- Author
-
Ishimura A, Ogawa C, Yatabe M, Tani K, and Inoue M
- Subjects
- Viscosity, Humans, Injections, Elasticity, Drug Compounding, Chemistry, Pharmaceutical, Ointments, Drugs, Generic administration & dosage, Drugs, Generic chemistry, Rheology
- Abstract
Generic medications contain the identical active ingredient in the same concentration as their branded counterparts and are administered in the same manner, aiming to deliver comparable efficacy, dosage, and clinical outcomes. Nevertheless, variations in additives and formulation processes, particularly noticeable in topical medications, can influence factors like ease of use and patient adherence. Therefore, in this study, we aimed to compare the rheological attributes of branded and generic injectable ointments, assessing disparities in formulation performance and their impact on patient care. Posterisan
® Forte and Hemoporison® ointments were used as the branded and generic versions, respectively, and their viscosity, ductility, and viscoelastic properties were evaluated. Posterisan® Forte showcased enhanced spread ability, maintaining uniform flow characteristics across varying temperatures, whereas Hemoporison® displayed pronounced thixotropic properties and stiffness, suggesting potential benefits for applications necessitating reversible viscosity adjustments and heightened rigidity. Despite sharing identical additives, observable differences in physical characteristics highlight the necessity of understanding formulation traits, which could influence ointment behavior. Alterations in fluidity and viscosity may affect how patients perceive and apply the medication, potentially influencing treatment outcomes and the occurrence of adverse effects.- Published
- 2024
- Full Text
- View/download PDF
4. Revisiting Niclosamide Formulation Approaches - a Pathway Toward Drug Repositioning.
- Author
-
Jug M, Laffleur F, and Millotti G
- Subjects
- Humans, Drug Compounding, Solubility, Animals, Nanoparticles chemistry, Anthelmintics chemistry, Anthelmintics pharmacokinetics, Anthelmintics pharmacology, Anthelmintics administration & dosage, Chemistry, Pharmaceutical, Drug Repositioning, Niclosamide pharmacology, Niclosamide chemistry, Niclosamide pharmacokinetics, Niclosamide administration & dosage, Biological Availability
- Abstract
Niclosamide (NIC), an anthelmintic drug, has garnered recent attention for its potential as an antiviral, antibacterial, and chemotherapeutic agent, among other applications. Repurposing NIC presents a current trend, offering significant time and cost savings compared to developing entirely new therapeutic chemical entities. However, its drawback lies in poor solubility, resulting in notably low oral bioavailability. This review consolidates efforts to overcome this limitation by summarizing twelve categories of formulations, spanning derivatives, amorphous solid dispersions, co-crystals, nanocrystals, micelles, nanohybrids, lipid nanoparticles and emulsions, cyclodextrins, polymeric nanoparticles, dry powders for inhalation, 3D printlets, and nanofibers. These formulations cover oral, injectable, inhalable and potentially (trans)dermal routes of administration. Additionally, we present a comprehensive overview of NIC characteristics, including physico-chemical properties, metabolism, safety, and pharmacokinetics. Moreover, we identify gaps in formulation and administration pathways that warrant further investigation to address NIC poor bioavailability., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Jug et al.)
- Published
- 2024
- Full Text
- View/download PDF
5. Biological and Medicinal Chemistry Sector of The Royal Society of Chemistry: Promoting Chemistry Learning, Networking and Excellence for Baby Boomers through to Gen Alpha!
- Author
-
Bagal SK, Giblin GMP, Hall A, and Jones PS
- Subjects
- Humans, Societies, Scientific, United Kingdom, Chemistry, Pharmaceutical
- Abstract
The Biological and Medicinal Chemistry Sector (BMCS) is an important interest group within the UK's Royal Society of Chemistry (RSC). Operating through a committee of voluntary members, the main goal of the BMCS is to share knowledge within the sector, primarily by organizing high quality scientific meetings, with a particular focus on networking. Financial support and tailored scientific programmes encourage training and development across multiple generations, from school age through to retirement. Scientific excellence is recognised through several high-profile awards., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
6. Seven-membered N-heterocycles as approved drugs and promising leads in medicinal chemistry as well as the metal-free domino access to their scaffolds.
- Author
-
Leśniewska A and Przybylski P
- Subjects
- Humans, Azepines chemistry, Azepines pharmacology, Azepines chemical synthesis, Chemistry, Pharmaceutical, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents chemical synthesis, Molecular Structure, Animals, Drug Approval, Stereoisomerism, Heterocyclic Compounds chemistry, Heterocyclic Compounds pharmacology, Heterocyclic Compounds chemical synthesis
- Abstract
Azepanes or azepines are structural motifs of many drugs, drug candidates and evaluated lead compounds. Even though compounds having N-heterocyclic 7-membered rings are often found in nature (e.g. alkaloids), the natural compounds of this group are rather rare as approved therapeutics. Thus, recently studied and approved azepane or azepine-congeners predominantly consist of semi-synthetically or synthetically-obtained scaffolds. In this review a comparison of approved drugs and recently investigated leads was proposed taking into regard their structural aspects (stereochemistry), biological activities, pharmacokinetic properties and confirmed molecular targets. The 7-membered N-heterocycles reveal a wide range of biological activities, not only against CNS diseases, but also as e.g. antibacterial, anticancer, antiviral, antiparasitic and against allergy agents. As most of the approved or investigated potential drugs or lead structures, belonging to 7-membered N-heterocycles, are synthetic scaffolds, this report also reveals different and efficient metal-free cascade approaches useful to synthesize both simple azepane or azepine-containing congeners and those of oligocyclic structures. Stereochemistry of azepane/azepine fused systems, in view of biological data and binding with the targets, is discussed. Apart from the approved drugs, we compare advances in SAR studies of 7-membered N-heterocycles (mainly from 2018 to 2023), whereas the related synthetic part concerning various domino strategies is focused on the last ten years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
7. The U.S. FDA approved cardiovascular drugs from 2011 to 2023: A medicinal chemistry perspective.
- Author
-
Jiang Y, Liu P, Qiu Z, Zhou M, Cheng M, and Yang T
- Subjects
- Humans, United States, United States Food and Drug Administration, Drug Approval, Cardiovascular Agents chemistry, Cardiovascular Agents pharmacology, Cardiovascular Agents therapeutic use, Cardiovascular Diseases drug therapy, Chemistry, Pharmaceutical
- Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. A total of 28 new molecular entities (NMEs) were approved by the U.S. Food and Drug Administration (FDA) for the treatment of cardiovascular diseases from 2011 to 2023. Approximately 25 % of the medications were sanctioned for the management of diverse vascular disorders. The other major therapeutic areas of focus included antilipemic agents (15 %), blood pressure disease (11 %), heart failure, hyperkalemia, and cardiomyopathy (7-8% each). Among all the approved drugs, there are a total of 22 new chemical entities (NCEs), including inhibitors, agonists, polymers, and inorganic compounds. In addition to NCEs, 6 biological agents (BLAs), including monoclonal antibodies, small interfering RNAs (siRNAs), and antisense oligonucleotides, have also obtained approval for the treatment of cardiovascular diseases. From this perspective, approved NCEs are itemized and discussed based on their disease, targets, chemical classes, major drug metabolites, and biochemical and pharmacological properties. Systematic analysis has been conducted to examine the binding modes of these approved drugs with their targets using cocrystal structure information or docking studies to provide valuable insights for designing next-generation agents. Furthermore, the synthetic approaches employed in the creation of these drug molecules have been emphasized, aiming to inspire the development of novel, efficient, and applicable synthetic methodologies. Generally, the primary objective of this review is to provide a comprehensive examination of the clinical applications, pharmacology, binding modes, and synthetic methodologies employed in small-molecule drugs approved for treating CVD. This will facilitate the development of more potent and innovative therapeutics for effectively managing cardiovascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
8. Organoselenium Compounds in Medicinal Chemistry.
- Author
-
Gallo-Rodriguez C and Rodriguez JB
- Subjects
- Humans, Chemistry, Pharmaceutical, Molecular Structure, Animals, Antioxidants chemistry, Antioxidants pharmacology, Organoselenium Compounds chemistry, Organoselenium Compounds pharmacology
- Abstract
The chemical and biological interest in this element and the molecules bearing selenium has been exponentially growing over the years. Selenium, formerly designated as a toxin, becomes a vital trace element for life that appears as selenocysteine and its dimeric form, selenocystine, in the active sites of selenoproteins, which catalyze a wide variety of reactions, including the detoxification of reactive oxygen species and modulation of redox activities. From the point of view of drug developments, organoselenium drugs are isosteres of sulfur-containing and oxygen-containing drugs with the advantage that the presence of the selenium atom confers antioxidant properties and high lipophilicity, which would increase cell membrane permeation leading to better oral bioavailability. This statement is the paramount relevance considering the big number of clinically employed compounds bearing sulfur or oxygen atoms in their structures including nucleosides and carbohydrates. Thus, in this article we have focused on the relevant features of the application of selenium in medicinal chemistry. With the increasing interest in selenium chemistry, we have attempted to highlight the most significant published data on this subject, mainly concentrating the analysis on the last years. In consequence, the recent advances of relevant pharmacological organoselenium compounds are discussed., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
9. Recent contributions of pyridazine as a privileged scaffold of anticancer agents in medicinal chemistry: An updated review.
- Author
-
Liu ZQ, Zhang Q, Liu YL, Yu XQ, Chui RH, Zhang LL, Zhao B, and Ma LY
- Subjects
- Humans, Structure-Activity Relationship, Chemistry, Pharmaceutical, Molecular Structure, Neoplasms drug therapy, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Pyridazines chemistry, Pyridazines pharmacology, Pyridazines chemical synthesis, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis
- Abstract
Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure-activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
10. Development of engineered transferosomal gel containing meloxicam for the treatment of osteoarthritis.
- Author
-
Maheshwari R, Sharma M, and Chidrawar VR
- Subjects
- Animals, Particle Size, Drug Delivery Systems, Drug Stability, Skin Absorption, Chemistry, Pharmaceutical, Meloxicam administration & dosage, Gels, Osteoarthritis drug therapy, Thiazoles administration & dosage, Thiazines administration & dosage, Thiazines therapeutic use, Liposomes, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Drug Liberation
- Abstract
Objective: .In this study, we investigated the potential of meloxicam (MLX) developed as transferosomal gel as a novel lipidic drug delivery system to address osteoarthritis (OTA), a degenerative joint disease that causes pain and stiffness. By incorporating meloxicam into a transferosomal gel, our aim was to provide a targeted and efficient delivery system capable of alleviating symptoms and slowing down the progression of OTA., Material and Methods: Classical lipid film hydration technique was utilized to formulate different transferosomal formulations. Different transferosomal formulations were prepared by varying the molar ratio of phospholipon-90H (phosphodylcholine) to DSPE (50:50, 60:40, 70:30, 80:20, and 90:10) and per batch, 80mg of total lipid was used. The quality control parameters such as entrapment efficiency, particle size and morphology, polydispersity and surface electric charge, in vitro drug release, ex vivo permeation and stability were measured., Results: The optimized transferosomal formulations revealed a small vesicle size (121±12nm) and greater MLX entrapment (68.98±2.3%). Transferosomes mediated gel formulation MLX34 displayed pH (6.3±0.2), viscosity (6236±12.3 cps), spreadability (13.77±1.77 gm.cm/sec) and also displayed sustained release pattern of drug release (81.76±7.87% MLX released from Carbopol-934 gel matrix in 24h). MLX34 revealed close to substantial anti-inflammatory response, with ∼81% inhibition of TNF-α in 48h. Physical stability analysis concluded that refrigerator temperature was the preferred temperature to store transferosomal gel., Conclusion: MLX loaded transferosomes containing gel improved the skin penetration and therefore resulted into increased inhibition of TNF-α level., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
11. A promising future of metal-N-heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents.
- Author
-
Zhao Q, Han B, Peng C, Zhang N, Huang W, He G, and Li JL
- Subjects
- Humans, Coordination Complexes chemistry, Coordination Complexes pharmacology, Coordination Complexes chemical synthesis, Chemistry, Pharmaceutical, Animals, Apoptosis drug effects, Neoplasms drug therapy, Organometallic Compounds chemistry, Organometallic Compounds pharmacology, Metals chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Methane analogs & derivatives, Methane chemistry, Methane pharmacology, Heterocyclic Compounds chemistry, Heterocyclic Compounds pharmacology
- Abstract
Metal complexes based on N-heterocyclic carbene (NHC) ligands have emerged as promising broad-spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal-NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified. However, a comprehensive review of their biological mechanisms is currently absent. In general, apoptosis caused by metal-NHCs is common in tumor cells. They can cause a series of changes after entering cells, such as mitochondrial membrane potential (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, and caspase activation, ultimately leading to apoptosis. Therefore, a detailed understanding of the influence of metal-NHCs on cancer cell apoptosis is crucial. In this review, we provide a comprehensive summary of recent advances in metal-NHC complexes that trigger apoptotic cell death via different apoptosis-related targets or signaling pathways, including B-cell lymphoma 2 (Bcl-2 family), p53, cyt c, ER stress, lysosome damage, thioredoxin reductase (TrxR) inhibition, and so forth. We also discuss the challenges, limitations, and future directions of metal-NHC complexes to elucidate their emerging application in medicinal chemistry., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
12. A new approach to drug intravenous compatibility research: the case of obstetric parenteral drugs.
- Author
-
Leeuwerik AF, van Merendonk LN, de Boer MA, Wilhelm AJ, Kolkman A, and Bet PM
- Subjects
- Humans, Female, Pregnancy, Infusions, Intravenous, Drug Combinations, Infusions, Parenteral standards, Infusions, Parenteral methods, Drug Incompatibility
- Abstract
Objectives: The product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these drugs over one lumen for this group of patients. Therefore, this study focuses on Y-site compatibility. Since different conditions between clinical and laboratory settings can lead to discrepancies in results, a novel approach for drug intravenous compatibility testing was designed to reflect clinical conditions. The aim was to study the compatibility of nine commonly used drug pairs in obstetrics and to evaluate the clinical value of the designed method., Methods: The clinical situation was reflected by using different temperature ranges (20°C and 37°C), actual Y-site flow ratios, clinically relevant drug pairs and an observation time of 120 min. The clinically relevant drugs pairs include atosiban, nicardipine, amoxicillin/clavulanic acid, oxytocin, remifentanil, labetalol and magnesium sulpfate. Drug pairs were visually assessed according to the European Pharmacopoeia (Ph. Eur.) and pH was measured. When incompatibility of a drug pair seemed likely based on literature review or observed abnormalities during visual assessment, subvisual analysis was performed using a particle counter. Y-site compatibility applied for drug pairs when no visual changes occurred or when no additional particles were formed during the observation time., Results: Eight of the nine combinations showed no visual changes or noticeable changes in pH during the observation time. The amoxicillin/clavulanic-acid-oxytocin combination showed a colour change at 37°C at the actual Y-site flow ratio. However, subvisual particle counting showed no formation of additional particles., Conclusions: Y-site compatibility was established for all tested drug pairs. The new clinical approach for analysing Y-site compatibility provides a high certainty of outcomes for clinical practice. In this way, clinical complications and use of several additional intravenous catheters can be avoided., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
13. Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects.
- Author
-
Aebi J, Atz K, Ametamey SM, Benz J, Blaising J, Butini S, Campiani G, Carreira EM, Collin L, De Lago E, Gazzi T, Gertsch J, Gobbi L, Guba W, Fernández-Ruiz J, Fingerle J, Haider A, He Y, Heitman LH, Honer M, Hunziker D, Kuhn B, Maccarrone M, Märki HP, Martin RE, Mohr P, Mu L, Nazaré M, Nippa DF, Oddi S, O'Hara F, Pacher P, Romero J, Röver S, Rufer AC, Schibli R, Schneider G, Stepan AF, Sykes DA, Ullmer C, Van der Stelt M, Veprintsev DB, Wittwer MB, and Grether U
- Subjects
- Humans, Drug Industry, Monoacylglycerol Lipases metabolism, Monoacylglycerol Lipases antagonists & inhibitors, Drug Development, Academia, Drug Discovery, Endocannabinoids metabolism, Endocannabinoids chemistry, Chemistry, Pharmaceutical
- Abstract
The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples., (Copyright 2024 Johannes Aebi, Kenneth Atz, Simon M. Ametamey, Jörg Benz, Julie Blaising, Stefania Butini, Giuseppe Campiani, Erick M. Carreira, Ludovic Collin, Eva de Lago, Thais Gazzi, Jürg Gertsch, Luca Gobbi, Wolfgang Guba, Javier Fernández-Ruiz, Jürgen Fingerle, Ahmed Haider, Yingfang He, Laura H. Heitman, Michael Honer, Daniel Hunziker, Bernd Kuhn, Mauro Maccarrone, Hans Peter Märki, Rainer E. Martin, Peter Mohr, Linjing Mu, Marc Nazaré, David F. Nippa, Sergio Oddi, Fionn O’Hara, Pal Pacher, Julian Romero, Stephan Röver, Arne C. Rufer, Roger Schibli, Gisbert Schneider, Antonia F. Stepan, David A. Sykes, Christoph Ullmer, Mario van der Stelt, Dmitry B. Veprintsev, Matthias B. Wittwer, Uwe Grether. License: This work is licensed under a Creative Commons Attribution 4.0 International License.)
- Published
- 2024
- Full Text
- View/download PDF
14. Medicinal chemistry aspects of fat mass and obesity associated protein: structure, function and inhibitors.
- Author
-
Ren C, Cao Z, Liu Y, Wang R, Lin C, and Wang Z
- Subjects
- Humans, Structure-Activity Relationship, Obesity drug therapy, Obesity metabolism, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Neoplasms drug therapy, Neoplasms metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Animals, Molecular Structure, Alpha-Ketoglutarate-Dependent Dioxygenase FTO antagonists & inhibitors, Alpha-Ketoglutarate-Dependent Dioxygenase FTO metabolism, Chemistry, Pharmaceutical
- Abstract
Adiposity and obesity-related proteins (FTO), the earliest identified mRNA N
6 -methyladenosine (m6 A) demethylases, are known to play crucial roles in several biological processes. Therefore, FTO is a promising target for anticancer treatment. Understanding the biological functions and regulatory mechanisms of FTO targets can serve as guidelines for drug development. Despite significant efforts to develop FTO inhibitors, no specific small-molecule inhibitors have entered clinical trials so far. In this manuscript, we review the relationship between FTO and various cancers, the small-molecule inhibitors developed against FTO targets from the perspective of medicinal chemistry and other fields, and describe their structural optimization process and structure-activity relationship, providing clues for their future development direction.- Published
- 2024
- Full Text
- View/download PDF
15. Formulation of hesperidin-loaded in situ gel for ocular drug delivery: a comprehensive study.
- Author
-
Gözcü S, Polat HK, Gültekin Y, Ünal S, Karakuyu NF, Şafak EK, Doğan O, Pezik E, Haydar MK, Aytekin E, Kurt N, and Laçin BB
- Subjects
- Animals, Humans, Citrus sinensis chemistry, Conjunctivitis, Allergic drug therapy, Drug Compounding, Viscosity, Mice, Plant Extracts chemistry, Plant Extracts pharmacology, Cell Survival drug effects, Chemistry, Pharmaceutical, Hesperidin chemistry, Hesperidin pharmacology, Hesperidin analogs & derivatives, Drug Delivery Systems, Gels chemistry
- Abstract
Background: Allergic conjunctivitis is one of the most common eye disorders. Different drugs are used for its treatment. Hesperidin is an active substance isolated from Citrus sinensis L. (Rutaceae) fruit peels, with known anti-inflammatory activity but low solubility. It was complexed with cyclodextrin and encapsulated in situ gel to extend its duration in the eye., Results: The optimized formulation comprised 1% hesperidin, 1.5% hydroxyethyl cellulose, and 16% poloxamer 407. The viscosity at 25 °C was 492 ± 82 cP, and at 35 °C it was 8875 ± 248 cP, the pH was 7.01 ± 0.03, gelation temperature was 34 ± 1.3 °C, and gelation time was 33 ± 1.2 s. There was a 66% in vitro release in the initial 2 h, with a burst effect. A lipoxygenase (LOX) inhibition test determined that hesperidin was active at high doses on leukotyrens seen in the body in allergic diseases. In cell-culture studies, the hesperidin cyclodextrin complex loaded in situ gel, BRN9-CD (poloxamer 16%, hydroxy ethyl cellulose (HEC) 1.5%), enhanced cell viability in comparison with the hesperidin solution. It was determined that BRN9-CD did not cause any irritation in the ocular tissues in the Draize test., Conclusion: The findings of this study demonstrate the potential of the in situ gel formulation of hesperidin in terms of ease of application and residence time on the ocular surface. Due to its notable LOX inhibition activity and positive outcomes in the in vivo Draize test, it appears promising for incorporation into pharmaceutical formulations. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)
- Published
- 2024
- Full Text
- View/download PDF
16. Dual-target EZH2 inhibitor: latest advances in medicinal chemistry.
- Author
-
Wei L, Mei D, Hu S, and Du S
- Subjects
- Humans, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Neoplasms drug therapy, Neoplasms metabolism, Structure-Activity Relationship, Chemistry, Pharmaceutical, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Animals, Transcription Factors antagonists & inhibitors, Transcription Factors metabolism, Enhancer of Zeste Homolog 2 Protein antagonists & inhibitors, Enhancer of Zeste Homolog 2 Protein metabolism
- Abstract
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, plays a crucial role in tumor progression by regulating gene expression. EZH2 inhibitors have emerged as promising anti-tumor agents due to their potential in cancer treatment strategies. However, single-target inhibitors often face limitations such as drug resistance and side effects. Dual-target inhibitors, exemplified by EZH1/2 inhibitor HH-2853( 28 ), offer enhanced efficacy and reduced adverse effects. This review highlights recent advancements in dual inhibitors targeting EZH2 and other proteins like BRD4, PARP1, and EHMT2, emphasizing rational design, structure-activity relationships, and safety profiles, suggesting their potential in clinical applications.
- Published
- 2024
- Full Text
- View/download PDF
17. FAK inhibitors in cancer, a patent review - an update on progress.
- Author
-
Ye YX, Cao YY, Xu LS, Wang HC, Liu XH, and Zhu HL
- Subjects
- Animals, Humans, Chemistry, Pharmaceutical, Drug Development, Molecular Targeted Therapy, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Drug Design, Focal Adhesion Protein-Tyrosine Kinases antagonists & inhibitors, Focal Adhesion Protein-Tyrosine Kinases metabolism, Neoplasms drug therapy, Neoplasms pathology, Neoplasms enzymology, Patents as Topic, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors chemistry
- Abstract
Introduction: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation., Areas Covered: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research., Expert Opinion: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.
- Published
- 2024
- Full Text
- View/download PDF
18. Boosting the Impact of EFMC Young Scientists Network Through the Creation of Working Groups.
- Author
-
Mari M, Lanthier C, Proj M, Donckele EJ, Josa-Culleré L, Goncharenko K, Leroy S, Matagne B, McKenna SM, and Borsari C
- Subjects
- Humans, Europe, Research Personnel, Chemistry, Pharmaceutical
- Abstract
The establishment of the Young Scientists Network (YSN) by the European Federation for Medicinal Chemistry (EFMC) served as a proactive response to the evolving landscape of the scientific community. The YSN aims to assist early-career medicinal chemists and chemical biologists by responding to emerging themes, such as the influence of social media, shifts in gender balance within the scientific population, and evolving educational opportunities. The YSN also ensures that the upcoming generation of scientists actively contributes to shape the EFMC's strategic direction while addressing their specific needs. Initially conceived as a general concept, YSN has evolved into a proactive and dynamic team which demonstrates a tangible impact. To boost the impact of the YSN and involve additional motivated young scientists, we have adopted a novel organization, and structured the team in seven working groups (WGs). Herein, we will discuss the tasks of the different WGs as well as the activities planned for the near future. We believe this structure will strengthen the pivotal role YSN has already played in serving medicinal chemists and chemical biologists in Europe. The YSN now has the structure and motivation to pave the way to attract young scientists across Europe and to give them the stage within EFMC., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
19. Benzimidazole-Oxadiazole Hybrids-Development in Medicinal Chemistry: An Overview.
- Author
-
Bhat RM, Hegde V, Budagumpi S, Adimule V, and Keri RS
- Subjects
- Humans, Structure-Activity Relationship, Chemistry, Pharmaceutical, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Drug Discovery, Antioxidants chemistry, Antioxidants pharmacology, Oxadiazoles chemistry, Oxadiazoles pharmacology, Benzimidazoles chemistry, Benzimidazoles pharmacology
- Abstract
To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety's potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole-oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti-inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole-oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure-activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole-oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
20. Long-term stability of esketamine in polypropylene syringes at 5 ± 3°C.
- Author
-
Kinet-Poleur A, Colsoul ML, Catry E, Bihin BP, Sneyers BE, Hubert J, Jamart J, Soumoy L, Galanti LM, Hecq JD, and Closset M
- Abstract
Objective: Esketamine (Vesierra) is a molecule, used alone or in combination, to induce and maintain general anaesthesia and to relieve pain in emergency medicine. The aim of this study is to evaluate the long-term physicochemical stability of a 1 mg/mL solution of esketamine diluted in 0.9% sodium chloride (NaCl) and stored in polypropylene syringes at 5±3°C during 65 days (64+1 day at 22±3°C) and 72 hours at 22±3°C (room temperature), in order to centralise preparation under aseptic conditions in hospital pharmacy., Methods: Ten syringes were prepared under aseptic conditions. Five syringes were stored at 22±3°C for 3 days, and the five others were stored at 5±3°C for 64 days (+ 1 day at room temperature). The stability was periodically investigated. Particle appearance or colour changes were checked by visual inspection. A research of crystals was performed under the microscope. pH was followed to assess its stability. The turbidity of the solutions was estimated by a measure of optical densities at 350, 410 and 550 nm. The molecule concentrations were measured by ultra-high performance liquid chromatography (UHPLC) coupled with a photodiode array detection (PDA), using a newly developed method., Results: Based on microscopic examination, no crystals were observed, during the observation period. pH and absorbances at 350, 410 and 550 nm were also stable. Macroscopically, there was no change in colour and appearance of opacity, turbidity or precipitation. Statistical analysis indicates that 1 mg/mL esketamine solutions were chemically stable under these conditions, given that less than 5% of the solutions have lost more than 10% of their initial content during the study based on the prediction interval., Conclusions: One mg/mL solutions of esketamine hydrochloride are physically and chemically stable after production, for at least 72 hours at 22±3°C and 64 days at 5±3°C (+ 1 day at room temperature)., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
21. ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.
- Author
-
Fougiaxis V, He B, Khan T, Vatinel R, Koutroumpa NM, Afantitis A, Lesire L, Sierocki P, Deprez B, and Deprez-Poulain R
- Subjects
- Animals, Humans, Autoimmune Diseases drug therapy, Autoimmune Diseases immunology, Autoimmunity drug effects, Chemistry, Pharmaceutical, Protease Inhibitors pharmacology, Protease Inhibitors chemistry, Protease Inhibitors therapeutic use, Histocompatibility Antigens Class I, Aminopeptidases antagonists & inhibitors, Aminopeptidases metabolism, Minor Histocompatibility Antigens metabolism, Minor Histocompatibility Antigens immunology
- Abstract
Endoplasmic reticulum aminopeptidases ERAP1 and 2 are intracellular aminopeptidases that trim antigenic precursors and generate antigens presented by major histocompatibility complex class I (MHC-I) molecules. They thus modulate the antigenic repertoire and drive the adaptive immune response. ERAPs are considered as emerging targets for precision immuno-oncology or for the treatment of autoimmune diseases, in particular MHC-I-opathies. This perspective covers the structural and biological characterization of ERAP, their relevance to these diseases and the ongoing research on small-molecule inhibitors. We describe the chemical and pharmacological space explored by medicinal chemists to exploit the potential of these targets given their localization, biological functions, and family depth. Specific emphasis is put on the binding mode, potency, selectivity, and physchem properties of inhibitors featuring diverse scaffolds. The discussion provides valuable insights for the future development of ERAP inhibitors and analysis of persisting challenges for the translation for clinical applications.
- Published
- 2024
- Full Text
- View/download PDF
22. Cleaning validation for blister packaging machines in hospital-supplying pharmacies.
- Author
-
Fenske D, Zerrenner L, and Zergiebel S
- Abstract
Objective: To ensure quality-assured care for patients, validation of a cleaning process for blister machines is essential. Due to the high operating costs of maintaining high-performance liquid chromatography (HPLC) which is mainly used for this type of analysis, a new, quick and cost-effective analysis method using UV-Vis spectroscopy has been developed., Method: Marker substances (metamizole (dipyrone) and paracetamol tablets) were packed in blisters. Afterwards test tablets were packaged before and after cleaning the blister machine and examined for contamination using UV-Vis spectroscopy., Results: UV-Vis spectroscopy has been shown to be superior to HPLC analysis for cleaning validation of blister machines, as it is much faster and cheaper, requires less equipment and personnel effort, while maintaining the same reliability and sensitivity., Conclusion: Unit-dose blistering is becoming increasingly popular in the daily routine of hospital pharmacies worldwide due to a variety of advantages. Therefore, cleaning validation of blistering machines has become a mandatory duty of care. The UV-Vis spectroscopic method presented here is the first innovative method suitable for the cleaning validation of blister machines to date., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
23. Asymmetric Carbene Transfer: Enhancing Chemical Diversity for Drug Discovery.
- Author
-
Shi T and Hu W
- Subjects
- Stereoisomerism, Chemistry, Pharmaceutical, Humans, Methane analogs & derivatives, Methane chemistry, Drug Discovery, Biological Products chemistry
- Abstract
The quest to explore chemical space is vital for identifying novel disease targets, impacting both the effectiveness and safety profile of therapeutic agents. The tangible chemical space, currently estimated at a conservative 10
8 synthesized compounds, pales in comparison to the theoretically conceivable diversity of 1060 molecules. To bridge this vast gap, organic chemists are spearheading innovative methodologies that promise to broaden this limited chemical diversity. A beacon of this progressive wave is Asymmetric Carbene Transfer (ACT), a burgeoning strategy that significantly boosts molecular diversity with efficient bond-formation and precise chiral control. This review focuses on the capabilities of ACT in creating pharmaceutically significant molecules, encompassing an array of natural products and bioactive compounds. Through the lens of ACT, we discern its substantial influence on drug discovery, paving the way for novel therapeutic avenues by expanding the boundaries of molecular diversity. This review will shed light on prospective methodological developments of ACT and articulate their conceivable contributions to the medicinal chemistry arena., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
- Full Text
- View/download PDF
24. Bioisosteric heterocyclic analogues of natural bioactive flavonoids by scaffold-hopping approaches: State-of-the-art and perspectives in medicinal chemistry.
- Author
-
La Monica G, Bono A, Alamia F, Lauria A, and Martorana A
- Subjects
- Humans, Chemistry, Pharmaceutical, Biological Products chemistry, Biological Products pharmacology, Biological Products chemical synthesis, Molecular Structure, Structure-Activity Relationship, Animals, Flavonoids chemistry, Flavonoids pharmacology, Flavonoids chemical synthesis, Heterocyclic Compounds chemistry, Heterocyclic Compounds pharmacology, Heterocyclic Compounds chemical synthesis
- Abstract
The flavonoid family is a set of well-known bioactive natural molecules, with a wide range of potential therapeutic applications. Despite the promising results obtained in preliminary in vitro/vivo studies, their pharmacokinetic and pharmacodynamic profiles are severely compromised by chemical instability. To address this issue, the scaffold-hopping approach is a promising strategy for the structural optimization of natural leads to discover more potent analogues. In this scenario, this Perspective provides a critical analysis on how the replacement of the chromon-4-one flavonoid core with other bioisosteric nitrogen/sulphur heterocycles might affect the chemical, pharmaceutical and biological properties of the resulting new chemical entities. The investigated derivatives were classified on the basis of their biological activity and potential therapeutic indications. For each session, the target(s), the specific mechanism of action, if available, and the key pharmacophoric moieties were highlighted, as revealed by X-ray crystal structures and in silico structure-based studies. Biological activity data, in vitro/vivo studies, were examined: a particular focus was given on the improvements observed with the new heterocyclic analogues compared to the natural flavonoids. This overview of the scaffold-hopping advantages in flavonoid compounds is of great interest to the medicinal chemistry community to better exploit the vast potential of these natural molecules and to identify new bioactive molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
25. MAATrica: a measure for assessing consistency and methods in medicinal and nutraceutical chemistry papers.
- Author
-
Panzarella G, Gallo A, Coecke S, Querci M, Ortuso F, Hofmann-Apitius M, Veltri P, Bajorath J, and Alcaro S
- Subjects
- Chemistry, Pharmaceutical, Humans, Semantics, Dietary Supplements analysis
- Abstract
The growing number of scientific papers and document sources underscores the need for methods capable of evaluating the quality of publications. Researchers who are looking for relevant papers for their studies need ways to assess the scientific value of these documents. One approach involves using semantic search engines that can automatically extract important knowledge from the growing body of text. In this study, we introduce a new metric called "MAATrica," which serves as the foundation for an innovative method designed to evaluate research papers. MAATrica offers a new way to analyze and categorize text, focusing on the consistency of research documents in the life sciences, particularly in the fields of medicinal and nutraceutical chemistry. This method utilizes semantic descriptions to cover in silico experiments, as well as in vitro and in vivo essays. Created to aid in evaluation processes like peer review, MAATrica uses toolkits and semantic applications to build the proposed measure, identify scientific entities, and gather information. We have applied MAATrica to roughly 90,000 papers and present our findings here., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GIULIA PANZARELLA reports financial support was provided by Magna Graecia University of Catanzaro Health Sciences Department. GIULIA PANZARELLA reports financial support was provided by DAAD - German Academic Exchange Service. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
26. My 50-Plus Years of Academic Research Collaborations with Industry. A Retrospective.
- Author
-
Hanessian S
- Subjects
- History, 20th Century, Drug Industry, History, 21st Century, Chemistry, Pharmaceutical, Biological Products chemistry, Biological Products chemical synthesis
- Abstract
A retrospective is presented highlighting the synthesis of selected "first-in-kind" natural products, their synthetic analogues, structure elucidations, and rationally designed bioactive synthetic compounds that were accomplished because of collaborations with past and present pharmaceutical and agrochemical companies. Medicinal chemistry projects involving structure-based design exploiting cocrystal structures of small molecules with biologically relevant enzymes, receptors, and bacterial ribosomes with synthetic small molecules leading to marketed products, clinical candidates, and novel drug prototypes were realized in collaboration. Personal reflections, historical insights, behind the scenes stories from various long-term projects are shared in this retrospective article.
- Published
- 2024
- Full Text
- View/download PDF
27. Significance of Triazole in Medicinal Chemistry: Advancement in Drug Design, Reward and Biological Activity.
- Author
-
Ajmal M, Mahato AK, Khan M, Rawat S, Husain A, Almalki EB, Alzahrani MA, Haque A, Hakme MJM, Albalawi AS, and Rashid M
- Subjects
- Humans, Chemistry, Pharmaceutical, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Animals, Molecular Structure, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents chemistry, Triazoles chemistry, Triazoles pharmacology, Triazoles chemical synthesis, Drug Design, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis
- Abstract
One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. Using computational simulations and models, we investigate the structure-activity relationships of 1,2,4-triazoles, showing how various modifications to the triazole core yield a variety of clinical therapeutic benefits. The review highlights the anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles' capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Coordinated efforts are required to translate the efficacy of 1,2,4-triazole compounds in preclinical models into practical therapeutic benefits. Based on the information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and the medical community as a whole. This comprehensive research, which is further reinforced by in-silico investigations, highlights the great medicinal potential of 1,2,4-triazoles. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
- Published
- 2024
- Full Text
- View/download PDF
28. Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective.
- Author
-
Chang X, Qu F, Li C, Zhang J, Zhang Y, Xie Y, Fan Z, Bian J, Wang J, Li Z, and Xu X
- Subjects
- Animals, Humans, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Proteolysis, Structure-Activity Relationship, Chemistry, Pharmaceutical
- Abstract
Unprecedented therapeutic targeting of previously undruggable proteins has now been achieved by molecular-glue-mediated proximity-induced degradation. As a small GTPase, G1 to S phase transition 1 (GSPT1) interacts with eRF1, the translation termination factor, to facilitate the process of translation termination. Studied demonstrated that GSPT1 plays a vital role in the acute myeloid leukemia (AML) and MYC-driven lung cancer. Thus, molecular glue (MG) degraders targeting GSPT1 is a novel and promising approach for treating AML and MYC-driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of GSPT1, highlighting the latest advances and challenges in MG degraders, as well as some representative patents. The structure-activity relationships, mechanism of action and pharmacokinetic features of MG degraders are emphasized to provide a comprehensive compendium on the rational design of GSPT1 MG degraders. We hope to provide an updated overview, and design guide for strategies targeting GSPT1 for the treatment of cancer., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
29. Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review.
- Author
-
Bendi A, Taruna, Rajni, Kataria S, Singh L, Kennedy JF, Supuran CT, and Raghav N
- Subjects
- Humans, Structure-Activity Relationship, Molecular Structure, Animals, Carbonic Anhydrase Inhibitors pharmacology, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors chemistry, Heterocyclic Compounds pharmacology, Heterocyclic Compounds chemistry, Heterocyclic Compounds chemical synthesis, Chemistry, Pharmaceutical, Carbonic Anhydrases metabolism, Carbonic Anhydrases drug effects
- Abstract
Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring the chemistry of various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) as one of the biologically active targets for curing various diseases. The widespread distribution of these enzymes and the high degree of homology shared by the different isoforms offer substantial challenges to discovering potential drugs. Medicinal and synthetic organic chemists have been continuously involved in developing CA inhibitors. This review explored the chemistry of different heterocycles as CA inhibitors using the last 11 years of published research work. It provides a pathway for young researchers to further explore the chemistry of a variety of synthetic as well as natural heterocycles as CA inhibitors., (© 2024 Deutsche Pharmazeutische Gesellschaft.)
- Published
- 2024
- Full Text
- View/download PDF
30. Specialised Pharmaceutical Formulation : The Science and Technology of Dosage Forms
- Author
-
Geoffrey D Tovey and Geoffrey D Tovey
- Subjects
- Pharmaceutical chemistry, Drug development, Chemistry, Pharmaceutical, Chimie pharmaceutique, Me´dicaments--De´veloppement
- Abstract
Formulation is a key step in the drug design process, where the active drug is combined with other substances that maximise the therapeutic potential, safety, and stability of the final medicinal product. Regulatory and quality demands, in addition to advances in processing technologies, result in growing challenges as well as possibilities for the field. Following on from Pharmaceutical Formulation, which covered traditional dosage forms such as tablets and capsules, this volume expands upon those formulations to cover a more diverse range of less common dosage forms. Novel routes of administration are covered from inhalational, dermal and transdermal formulations to ocular, oral suspensions, vaccines and nanoparticle drug delivery. The methods through which these formulations are processed and manufactured is also covered, providing essential knowledge to ensure quality, efficiency, and acceptable costing. Specialised Pharmaceutical Formulation is an essential, up to date resource for students and researchers working in academia and in the pharmaceutical industry and will equip readers with the ability to effectively and reliably produce products which can be approved, manufactured and made available to administer to patients.
- Published
- 2022
31. Medicinal Chemistry
- Author
-
Rudi van Eldik, Peter J. Sadler, Rudi van Eldik, and Peter J. Sadler
- Subjects
- Pharmaceutical chemistry, Chemistry, Pharmaceutical, Chimie pharmaceutique
- Abstract
Medicinal Chemistry, Volume 75, the latest release in the Advances in Inorganic Chemistry series, presents timely and informative summaries on current progress in a variety of subject areas. This acclaimed serial features reviews written by experts in the field, serving as an indispensable reference to advanced researchers that empowers readers to pursue new developments in each field. Users will find this to be a comprehensive overview of recent findings and trends from the last decade that covers various kinds of inorganic topics, from theoretical oriented supramolecular chemistry, to the quest for accurate calculations of spin states in transition metals. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Inorganic Chemistry series Includes the latest information on medicinal chemistry
- Published
- 2020
32. Genistein transfersome-embedded topical delivery system for skin melanoma treatment: in vitro and ex vivo evaluations.
- Author
-
Motawea A, Maria SN, Maria DN, Jablonski MM, and Ibrahim MM
- Subjects
- Humans, Drug Delivery Systems methods, Cell Line, Tumor, Drug Stability, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Antineoplastic Agents pharmacokinetics, Solubility, Drug Carriers chemistry, Chemistry, Pharmaceutical, Viscosity, Biological Availability, Administration, Cutaneous, Spheroids, Cellular drug effects, Genistein administration & dosage, Genistein pharmacology, Genistein pharmacokinetics, Melanoma drug therapy, Skin Neoplasms drug therapy, Particle Size, Drug Liberation, Hydrogels chemistry
- Abstract
Skin melanoma is considered the most dangerous form of skin cancer due to its association with high risk of metastasis, high mortality rate and high resistance to different treatment options. Genistein is a natural isoflavonoid with known chemotherapeutic activity. Unfortunately, it has low bioavailability due to its poor aqueous solubility and excessive metabolism. In the current study, genistein was incorporated into transferosomal hydrogel to improve its bioavailability. The prepared transferosomal formulations were characterized regarding: particle size; polydispersity index; zeta potential; encapsulation efficiency; TEM; FTIR; DSC; XRD; in vitro drug release; viscosity; pH; ex vivo anti-tumor activity on 3D skin melanoma spheroids and 1-year stability study at different storage temperatures. The optimized formulation has high encapsulation efficiency with an excellent particle size that will facilitate its penetration through the skin. The transfersomes have a spherical shape with sustained drug release profile. The anti-tumor activity evaluation of genistein transfersome revealed that genistein is a potent chemotherapeutic agent with enhanced penetration ability through the melanoma spheroids when incorporated into transfersomes. Stability study results demonstrate the high physical and chemical stability of our formulations. All these outcomes provide evidence that our genistein transferosomal hydrogel is a promising treatment option for skin melanoma.
- Published
- 2024
- Full Text
- View/download PDF
33. Thioamides in medicinal chemistry and as small molecule therapeutic agents.
- Author
-
Huang G, Cierpicki T, and Grembecka J
- Subjects
- Humans, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology, Small Molecule Libraries chemical synthesis, Animals, Molecular Structure, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Thioamides chemistry, Thioamides pharmacology, Thioamides chemical synthesis, Chemistry, Pharmaceutical
- Abstract
Thioamides, which are fascinating isosteres of amides, have garnered significant attention in drug discovery and medicinal chemistry programs, spanning peptides and small molecule compounds. This review provides an overview of the various applications of thioamides in small molecule therapeutic agents targeting a range of human diseases, including cancer, microbial infections (e.g., tuberculosis, bacteria, and fungi), viral infections, neurodegenerative conditions, analgesia, and others. Particular focus is given to design strategies of biologically active thioamide-containing compounds and their biological targets, such as kinases and histone methyltransferase ASH1L. Additionally, the review discusses the impact of the thioamide moiety on key properties, including potency, target interactions, physicochemical characteristics, and pharmacokinetics profiles. We hope that this work will offer valuable insights to inspire the future development of novel bioactive thioamide-containing compounds, facilitating their effective use in combating a wide array of human diseases., Competing Interests: Declaration of competing interest No conflict of interests exits in the submission of this manuscript, and manuscript is approved by all authors for publication. This work is the original research that has not been published previously, and not under consideration for publication elsewhere. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
34. Indole-core inhibitors of influenza a neuraminidase: iterative medicinal chemistry and molecular modeling.
- Author
-
Tsedilin A, Schmidtke M, Monakhova N, Leneva I, Falynskova I, Khrenova M, Lane TR, Ekins S, and Makarov V
- Subjects
- Animals, Dogs, Structure-Activity Relationship, Madin Darby Canine Kidney Cells, Molecular Structure, Models, Molecular, Influenza A virus drug effects, Influenza A virus enzymology, Dose-Response Relationship, Drug, Chemistry, Pharmaceutical, Humans, Mice, Microbial Sensitivity Tests, Virus Replication drug effects, Neuraminidase antagonists & inhibitors, Neuraminidase metabolism, Antiviral Agents pharmacology, Antiviral Agents chemistry, Antiviral Agents chemical synthesis, Indoles pharmacology, Indoles chemistry, Indoles chemical synthesis, Enzyme Inhibitors pharmacology, Enzyme Inhibitors chemistry, Enzyme Inhibitors chemical synthesis
- Abstract
Influenza viruses that cause seasonal and pandemic flu are a permanent health threat. The surface glycoprotein, neuraminidase, is crucial for the infectivity of the virus and therefore an attractive target for flu drug discovery campaigns. We have designed and synthesized more than 40 3-indolinone derivatives. We mainly investigated the role of substituents at the 2 position of the core as well as the introduction of substituents or a nitrogen atom in the fused phenyl ring of the core for inhibition of influenza virus neuraminidase activity and replication in vitro and in vivo. After evaluating the compounds for their ability to inhibit the viral neuraminidase, six potent inhibitors 3c, 3e, 7c, 12o, 12v, 18d were progressed to evaluate for cytotoxicity and inhibition of influenza virus A/PR/8/34 replication in in MDCK cells. Two hit compounds 3e and 12o were tested in an animal model of influenza virus infection. Molecular mechanism of the 3-indolinone derivatives interactions with the neuraminidase was revealed in molecular dynamic simulations. Proposed inhibitors bind to the 430-cavity that is different from the conventional binding site of commercial compounds. The most promising 3-indolinone inhibitors demonstrate stronger interactions with the neuraminidase in molecular models that supports proposed binding site., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
35. Advancing drug discovery: Thiadiazole derivatives as multifaceted agents in medicinal chemistry and pharmacology.
- Author
-
Babalola BA, Sharma L, Olowokere O, Malik M, and Folajimi O
- Subjects
- Humans, Structure-Activity Relationship, Chemistry, Pharmaceutical, Molecular Structure, Animals, Thiadiazoles chemistry, Thiadiazoles pharmacology, Thiadiazoles chemical synthesis, Drug Discovery
- Abstract
In this dispensation of rapid scientific and technological advancements, significant efforts are being made to curb health-related diseases. Research discoveries have highlighted the value of heterocyclic compounds, particularly thiadiazole derivatives, due to their diverse pharmacological activities. These compounds play a crucial role in therapeutic medicine and the development of effective drugs. Thiadiazoles are five-membered heterocyclic compounds consisting of one sulfur and two nitrogen atoms. This review explores advanced synthesis techniques, including the use of heterogeneous catalysts, microwave-assisted methods, ultrasound-assisted synthesis, solvent-free processes, multicomponent reactions, copper-catalyzed aerobic oxidative annulation, intramolecular cyclization, click-chemistry supported synthesis, and alkali-promoted, transition-metal-free mediated synthesis. These methods enhance the diversity and potential applications of thiadiazole compounds. Furthermore, this study provides up-to-date information on the key pharmacological activities of thiadiazole derivatives, highlighting their potential in therapeutic medicine for drug development. The structure-activity relationship (SAR) is also discussed to better understand their interactions and safety in biological systems. This work aims to expand on the reported chemistry and pharmacological potential of the thiadiazole moiety to validate their efficacy as promising pharmacophores in drug design and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
36. Discovery of an Azabicyclo[2.1.1]hexane Piperazinium Salt and Its Application in Medicinal Chemistry via a Rearrangement.
- Author
-
He C, Ba X, Shunatona HP, Edwards JT, Li YX, Keller TM, Sommer RD, Zapf CW, and Mortensen DS
- Subjects
- Molecular Structure, Chemistry, Pharmaceutical, Ligands, Salts chemistry, Piperazines chemistry, Piperazines chemical synthesis, Azabicyclo Compounds chemistry, Azabicyclo Compounds chemical synthesis
- Abstract
Herein we report the discovery of an azabicyclo[2.1.1]hexane piperazinium methanesulfonate salt from an unexpected rearrangement reaction in the preparation of ligand-directed degraders (LDDs). This bench-stable compound was found to be a versatile electrophile in a ring-opening reaction with various types of nucleophiles. Its utility as a versatile medicinal chemistry building block is further demonstrated in the synthesis of an LDD compound targeting degradation of the androgen receptor.
- Published
- 2024
- Full Text
- View/download PDF
37. Significance of Chalcone Scaffolds in Medicinal Chemistry.
- Author
-
Mazumder R, Ichudaule, Ghosh A, Deb S, and Ghosh R
- Subjects
- Humans, Chalcones chemistry, Chalcones pharmacology, Molecular Structure, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Chemistry, Pharmaceutical, Chalcone chemistry, Chalcone pharmacology
- Abstract
Chalcone is a simple naturally occurring α,β-unsaturated ketone with biological importance, which can also be easily synthesized in laboratories by reaction between two aromatic scaffolds. In plants, chalcones occur as polyphenolic compounds of different frameworks which are bioactive molecules that have been in traditional medicinal practice for many years. Chalcone-based lead molecules have been developed, possessing varied potentials such as antimicrobial, antiviral, anti-inflammatory, anticancer, anti-oxidant, antidiabetic, antihyperurecemic, and anti-ulcer effects. Chalcones contribute considerable fragments to give important heterocyclic molecules with therapeutic utilities targeting various diseases. These characteristic features have made chalcone a topic of interest among researchers and have attracted investigations into this widely applicable structure. This review highlights the extensive exploration carried out on the synthesis, biotransformations, chemical reactions, hybridization, and pharmacological potentials of chalcones, and aims to provide an extensive, thorough, and critical review of their importance, with emphasis on their properties, chemistry, and biomedical applications to boost future investigations into this potential scaffold in medicinal chemistry., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Published
- 2024
- Full Text
- View/download PDF
38. Performance evaluation of the HPLC diode array and evaporative light scattering detection for the implementation of dose-banded gemcitabine infusion bags.
- Author
-
Stalder T, Andre C, Ben Mahi M, Lethier L, Limat S, Legat C, and Guillaume Y
- Subjects
- Chromatography, High Pressure Liquid methods, Chromatography, High Pressure Liquid standards, Drug Packaging standards, Drug Packaging methods, Infusions, Intravenous methods, Infusions, Intravenous standards, Infusions, Intravenous instrumentation, Retrospective Studies, Humans, Scattering, Radiation, Light, Pharmacy Service, Hospital methods, Pharmacy Service, Hospital standards, Deoxycytidine analysis, Deoxycytidine analogs & derivatives, Gemcitabine, Antimetabolites, Antineoplastic analysis, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic standards
- Abstract
Background: Dose banding (DB) was used to optimise the individualisation of patient treatments with gemcitabine (Gem) in order to improve workload planning at the pharmacy of the University Hospital Centre of Besançon (UHCB). A new simple and fast high-performance liquid chromatographic (HPLC) method was also developed for the quantification of Gem without dilution of the infusion bags., Methods: Individual doses of Gem preparations were retrospectively analysed over a 1-year period to determine the frequency of prepared doses. Using a maximum gap of 7.5% around the doses chosen, the selected Gem standard doses were 1400 mg, 1600 mg, 1800 mg and 2000 mg. Following the DB scheme, the frequency of prescription of standard and individualised Gem doses was analysed over a period of 10 months. The four selected Gem standard doses were aseptically prepared in polyolefin infusion bags. Each series of 20 bags was stocked under refrigerated storage conditions (4°C) for up to 84 days. The quantification of Gem without dilution of the infusion bags was obtained by the development of a HPLC method coupled to a diode array detector (DAD) or an evaporative light scattering detector (ELSD)., Results: During the 10-month period following implementation of the DB, 75.6% of the 1266 prescribed doses were covered by the four standardised preparations. The number of different Gem doses was reduced from 183 to 55. Concerning the Gem quantification, both heteroscedasticity and non-linearity were observed with DAD. Using an ELSD, the trueness values were between 98.59% and 101.52% with excellent repeatability values between 0.66% and 1.42%., Conclusion: A new HPLC method has been developed for the quantification of Gem without dilution of the infusion bags prepared in advance as a result of a target DB scheme successfully implemented in our pharmacy department., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
39. Formulation and stability study of an oral paediatric phenobarbital 1% solution containing hydroxypropyl-β-cyclodextrins.
- Author
-
Parrenne L, Ribier Z, Abisror J, Cadix J, Benoit G, and Bordenave J
- Subjects
- Administration, Oral, Chromatography, High Pressure Liquid methods, Humans, Excipients chemistry, Child, Chemistry, Pharmaceutical methods, Chemistry, Pharmaceutical standards, Drug Compounding methods, Drug Compounding standards, Hydrogen-Ion Concentration, Phenobarbital chemistry, Phenobarbital analysis, 2-Hydroxypropyl-beta-cyclodextrin chemistry, Drug Stability, Anticonvulsants chemistry, Anticonvulsants administration & dosage, Anticonvulsants analysis, Pharmaceutical Solutions chemistry, Pharmaceutical Solutions standards, Pharmaceutical Solutions analysis
- Abstract
Objectives: Phenobarbital is a barbiturate, used to treat focal and generalised epilepsy. Since the end of marketing of the oral solution KANEURON in 2017, phenobarbital tablets remain the only available dosage form. Development of an oral phenobarbital solution for paediatric use is therefore essential to fulfil clinical needs. A new formulation of phenobarbital with hydroxypropyl-β-cyclodextrins (HPBCD) was developed, and the physicochemical stability of the solution was evaluated., Methods: Different excipients have been selected to formulate a solution of phenobarbital. Samples were dosed by High Performance Liquid Chromatography (HPLC) at 216 nm with a LiChroCART C18 endcapped column and mobile phase composed of phosphate buffer pH 3 and methanol (50:50 v/v). Linearity, accuracy, sensibility and specificity of the method were tested, and a forced degradation study was carried out. During stability study, content of phenobarbital, pH, osmolality of the phenobarbital solution and degradation products were followed up for 6 months in line with GERPAC guidelines., Results: The stability indicating the character of the assay method has been validated. The physicochemical stability study shows that the phenobarbital solution formulated is stable for 6 months, in line with International Conference of Harmonisation (ICH) recommendations Q1A and Q3B (R2) regarding the content of phenobarbital and levels of degradation products (no degradation products >0.01%). Phenobarbital concentration was 101.59±2.6% of initial concentration in refrigerated samples and 101.14±0.5% at 20±5°C. No phenobarbital degradation products (>0.01%) were observed throughout the 6 months. No significant variation of pH or osmolality was observed., Conclusions: HPBCD solubilise phenobarbital and create a homogeneous solution. These stability data set the shelf life of this new phenobarbital solution at up to 6 months. A microbiological stability study will be carried out to ensure the possibility of using this solution in children., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
40. Macrocyclization strategy for improving candidate profiles in medicinal chemistry.
- Author
-
Darlami O, Pun R, Ahn SH, Kim SH, and Shin D
- Subjects
- Humans, Cyclization, Drug Discovery, Molecular Structure, Chemistry, Pharmaceutical, Macrocyclic Compounds chemistry, Macrocyclic Compounds chemical synthesis, Macrocyclic Compounds pharmacology
- Abstract
Macrocycles are defined as cyclic compounds with 12 or more members. In medicinal chemistry, they are categorized based on their core chemistry into cyclic peptides and macrocycles. Macrocycles are advantageous because of their structural diversity and ability to achieve high affinity and selectivity towards challenging targets that are often not addressable by conventional small molecules. The potential of macrocyclization to optimize drug-like properties while maintaining adequate bioavailability and permeability has been emphasized as a key innovation in medicinal chemistry. This review provides a detailed case study of the application of macrocyclization over the past 5 years, starting from the initial analysis of acyclic active compounds to optimization of the resulting macrocycles for improved efficacy and drug-like properties. Additionally, it illustrates the strategic value of macrocyclization in contemporary drug discovery efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
41. From lab to nature: Recent advancements in the journey of gastroprotective agents from medicinal chemistry to phytotherapy.
- Author
-
Yadav S, Pandey A, and Mali SN
- Subjects
- Humans, Chemistry, Pharmaceutical, Anti-Ulcer Agents chemistry, Anti-Ulcer Agents pharmacology, Animals, Peptic Ulcer drug therapy, Phytotherapy
- Abstract
Peptic ulcer, affecting 10 % of the global population, results from imbalances in gastric juice pH and diminished mucosal defences. Key underlying factors are non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection, undermining mucosal resistance. Traditional treatments like proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists exhibit drawbacks such as adverse effects, relapses, and drug interactions. This review extensively explores the ethnomedicinal, synthetic and pharmacological facets of various potential peptic ulcer treatments. Rigorous methodologies involving electronic databases, and chemical structure verification via 'PubChem' and 'SciFinder' enhance the review's credibility. The provided information, spanning medicinal insights to intricate pharmacological mechanisms, establishes a robust groundwork for future research and the development of plant-derived or synthetic molecules for peptic ulcers, offering a promising alternative to conventional therapies., Competing Interests: Declaration of competing interest All the authors declare no conflict of interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
42. Solubilization of drugs using beta-cyclodextrin: Experimental data and modeling.
- Author
-
Kaboudi N, Asl SG, Nourani N, and Shayanfar A
- Subjects
- Pharmaceutical Preparations chemistry, Quantitative Structure-Activity Relationship, Hydrophobic and Hydrophilic Interactions, Hydrogen Bonding, Chemistry, Pharmaceutical, Solubility, beta-Cyclodextrins chemistry, Excipients chemistry
- Abstract
Many drug candidates fail to complete the entire drug development process because of poor physicochemical properties. Solubility is an important physicochemical property which plays a vital role in various stages of drug discovery and development. Several methods have been proposed to enhance the solubility of drugs, and complex formation with cyclodextrins is among them. Beta-cyclodextrin (βCD) is a common excipient for solubilization of drugs. The aim of this study is to develop the mechanistic QSPR models to predict the solubility enhancement of a drug in the presence of βCD. In this study, the solubility enhancement of some drugs in the presence of 10mM βCD at 25°C was experimentally determined or collected from the literature. Two different models to predict the solubilization by βCD were developed by binary logistic regression using structural properties of drugs with more than 80% accuracy. Polar surface area and excess molar refraction are the main parameters for estimating solubilization by βCD. Moreover, other descriptors related to hydrophobicity and the capability of hydrogen bonding formation of molecules could improve the accuracy of the established models., (Published by Elsevier Masson SAS.)
- Published
- 2024
- Full Text
- View/download PDF
43. The medicinal chemistry of piperazines: A review.
- Author
-
Faizan M, Kumar R, Mazumder A, Salahuddin, Kukreti N, Kumar A, and Chaitanya MVNL
- Subjects
- Humans, Structure-Activity Relationship, Animals, Piperazines chemistry, Piperazines chemical synthesis, Chemistry, Pharmaceutical
- Abstract
The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
44. Building respirable powder architectures: utilizing polysaccharides for precise control of particle morphology for enhanced pulmonary drug delivery.
- Author
-
Kadota K, Uchiyama H, Kämäräinen T, Tanaka S, and Tozuka Y
- Subjects
- Humans, Administration, Inhalation, Particle Size, Pharmaceutical Preparations administration & dosage, Pharmaceutical Preparations chemistry, Drug Compounding methods, Animals, Chemistry, Pharmaceutical, Metal-Organic Frameworks chemistry, Drug Delivery Systems, Dry Powder Inhalers, Polysaccharides chemistry, Powders, Lung metabolism, Excipients chemistry
- Abstract
Introduction: Dry powder inhaler (DPI) formulations are gaining attention as universal formulations with applications in a diverse range of drug formulations. The practical application of DPIs to pulmonary drugs requires enhancing their delivery efficiency to the target sites for various treatment modalities. Previous reviews have not explored the relation between particle morphology and delivery to different pulmonary regions. This review introduces new approaches to improve targeted DPI delivery using novel particle design such as supraparticles and metal-organic frameworks based on cyclodextrin., Areas Covered: This review focuses on the design of DPI formulations using polysaccharides, promising excipients not yet approved by regulatory agencies. These excipients can be used to design various particle morphologies by controlling their physicochemical properties and manufacturing methods., Expert Opinion: Challenges associated with DPI formulations include poor access to the lungs and low delivery efficiency to target sites in the lung. The restricted applicability of typical excipients contributes to their limited use. However, new formulations based on polysaccharides are expected to establish a technological foundation for the development of DPIs capable of delivering modalities specific to different lung target sites, thereby enhancing drug delivery.
- Published
- 2024
- Full Text
- View/download PDF
45. Stability of clozapine tablets repackaged in dose administration aids using repackaging machines.
- Author
-
Emonet M, Citterio-Quentin A, Bourgeois S, Godard V, Boidin C, Barratier C, and Boisramé J
- Abstract
Background: The use of dose administration aids in automated ward dispensing devices requires the repackaging of medications, which may impact their stability compared with the original manufacturer's packaging., Objectives: This study aimed to assess the physical and chemical stability of clozapine tablets for up to 84 days after repackaging., Methods: A total of 900 tablets of clozapine 100 mg (Viatris) were repackaged and stored under five different conditions to conduct physical and chemical stability tests on days 0, 28, 56 and 84. The results were compared with control tablets in their original packaging. Visual inspections of tablet appearance were performed. Physical tests included assessments of mass uniformity, friability and resistance to crushing, following the standards of the European Pharmacopoeia 11th edition. The chemical stability was determined using ultra-high performance liquid chromatography with tandem-mass spectrometry detection (UHPLC-MS/MS) to measure clozapine concentration, N-desmethyl-clozapine, and monitor clozapine degradation to detect formation of any degradation products other than N-desmethyl-clozapine., Results: Visual examination showed changes in the appearance of tablets only in those stored under UV light. Mass uniformity met standards for all tablets over 84 days. None passed the friability test due to tablet cracking after tumbling. A gradual deterioration in tablet hardness was observed with the resistance to crushing test. In terms of chemical stability, N-desmethyl-clozapine was undetected in any of the tablets stored under all conditions, and the mean concentration of clozapine remained within the target range over 84 days., Conclusion: N-desmethyl-clozapine was not detected and clozapine concentrations remained stable under all storage conditions. The tablets were compliant with the mass uniformity test in each condition. However, the tablets were cracked in the friability test and gradual deterioration in tablet hardness was observed. In the light of these results, the Vinatier Hospital pharmacy has chosen to establish a shelf life for clozapine tablets of 84 days., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
46. Interaction of Au(III) with amino acids: a vade mecum for medicinal chemistry and nanotechnology.
- Author
-
Mattioli EJ, Cipriani B, Zerbetto F, Marforio TD, and Calvaresi M
- Subjects
- Nanotechnology methods, Metal Nanoparticles chemistry, Chemistry, Pharmaceutical, Gold chemistry, Amino Acids chemistry
- Abstract
Au(III) is highly reactive. At odds with its reduced counterpart, Au(I), it is hardly present in structural databases. And yet, it is the starting reactant to form gold nanoclusters (AuNCs) and the constitutive component of a new class of drugs. Its reactivity is a world apart from that of the iso-electronic Pt(II) species. Rather than DNA, it targets proteins. Its interaction with amino acid residues is manifold. It can strongly interact with the residue backbones, amino acid side chains and protein ends, it can form appropriate complexes whose stabilization energy reaches up to more than 40 kcal mol
-1 , it can affect the p Ka of amino acid residues, and it can promote charge transfer from the residues to the amount that it is reduced. Here, quantum chemical calculations provide quantitative information on all the processes where Au(III) can be involved. A myriad of structural arrangements are examined in order to determine the strongest interactions and quantify the amount of charge transfer between protonated and deprotonated residues and Au(III). The calculated interaction energies of the amino acid side chains with Au(III) quantitatively reproduce the experimental tendency of Au(III) to interact with selenocysteine, cysteine and histidine and negatively charged amino acids such as Glu and Asp. Also, aromatic residues such as tyrosine and tryptophan strongly interact with Au(III). In proteins, basic pH plays a role in the deprotonation of cysteine, lysine and tyrosine and strongly increases the binding affinity of Au(III) toward these amino acids. The amino acid residues in the protein can also trigger the reduction of Au(III) ions. Sulfur-containing amino acids (cysteine and methionine) and selenocysteine provide almost one electron to Au(III) upon binding. Tyrosine also shows a considerable tendency to act as a reductant. Other amino acids, commonly identified in Au-protein adducts, such as Ser, Trp, Thr, Gln, Glu, Asn, Asp, Lys, Arg and His, possess a notable reducing power toward Au(III). These results and their discussion form a vade mecum that can find application in medicinal chemistry and nanotech applications of Au(III).- Published
- 2024
- Full Text
- View/download PDF
47. Gaucher Disease: A Glance from a Medicinal Chemistry Perspective.
- Author
-
Prencipe F, Barzan C, Savian C, Spalluto G, Carosati E, De Amici M, Mosconi G, Gianferrara T, Federico S, and Da Ros T
- Subjects
- Humans, Glucosyltransferases antagonists & inhibitors, Glucosyltransferases metabolism, Chemistry, Pharmaceutical, Glucosylceramidase antagonists & inhibitors, Glucosylceramidase metabolism, Glucosylceramidase chemistry, Enzyme Replacement Therapy, Molecular Structure, Gaucher Disease drug therapy, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Enzyme Inhibitors chemical synthesis
- Abstract
Rare diseases are particular pathological conditions affecting a limited number of people and few drugs are known to be effective as therapeutic treatment. Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, belongs to this class of disorders, and it is considered the most common among the Lysosomal Storage Diseases. The two main therapeutic approaches are the Enzyme Replacement Therapy (ERT) and the Substrate Reduction Therapy (SRT). ERT, consisting in replacing the defective enzyme by administering a recombinant enzyme, is effective in alleviating the visceral symptoms, hallmarks of the most common subtype of the disease whereas it has no effects when symptoms involve CNS, since the recombinant protein is unable to significantly cross the Blood Brain Barrier. The SRT strategy involves inhibiting glucosylceramide synthase (GCS), the enzyme responsible for the production of the associated storage molecule. The rational design of new inhibitors of GCS has been hampered by the lack of either the crystal structure of the enzyme or an in-silico model of the active site which could provide important information regarding the interactions of potential inhibitors with the target, but, despite this, interesting results have been obtained and are herein reviewed., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
48. Losartan potassium liquid formulation for paediatric hospital use: development and stability evaluation.
- Author
-
Corte AC, Gobetti C, Carlos G, de Oliveira Almeida SH, Ayres MV, Steppe M, and Garcia CV
- Abstract
Objectives: This study aimed to develop a liquid oral formulation containing losartan potassium, an angiotensin II receptor antagonist drug used for its antihypertensive activity, and to perform a preliminary stability assessment under different temperatures and packages to ensure paediatric therapeutic adherence and facilitate the hospital routine., Methods: A syrup containing losartan potassium (1.0 and 2.5 mg/mL) (excipients: potassium sorbate, sucrose (85%), water, citric acid and raspberry flavouring) was prepared. The packaging was carried out in amber polyethylene terephthalate (PET) and amber glass bottles (in triplicate) under the following conditions: (a) room temperature (15-30°C); (b) refrigeration (2-8°C); and (c) oven temperature (40°C) for 28 days. An analytical method by high performance liquid chromatography using a reverse-phase column was also developed and validated for quantitative determination of the drug in the formulations., Results: The analytical method showed satisfactory linearity, detection and quantification limits, precision, accuracy and robustness. Samples at room temperature maintained content values between 90% and 110% for 7 days, while those stored under refrigeration maintained a homogeneous appearance and content between 90% and 110% for a period of 21 days. Values of pH stayed in a narrow range. Viscosity results were between 40.1 and 49.2 centipoise (cp) for glass bottles and 42.4 and 54.7 cp for PET bottles., Conclusions: A simple and economical losartan potassium liquid formulation was produced and was shown to be stable under refrigeration for 21 days in both PET and glass packages., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
49. Medicinal chemistry strategies toward broad-spectrum antiviral agents to prevent next pandemics.
- Author
-
Lü Z, Dai X, Xu J, Liu Z, Guo Y, Gao Z, and Meng F
- Subjects
- Humans, Pandemics, COVID-19 Drug Treatment, COVID-19 epidemiology, Antiviral Agents chemistry, Antiviral Agents pharmacology, SARS-CoV-2 drug effects, Chemistry, Pharmaceutical
- Abstract
The pandemic and tremendous impact of severe acute respiratory syndrome coronavirus 2 alert us, despite great achievements in prevention and control of infectious diseases, we still lack universal and powerful antiviral strategies to rapidly respond to the potential threat of serious infectious disease. Various highly contagious and pathogenic viruses, as well as other unknown viruses may appear or reappear in human society at any time, causing a catastrophic epidemic. Developing broad-spectrum antiviral drugs with high security and efficiency is of great significance for timely meeting public health emergency and protecting the lives and health of the people. Hence, in this review, we summarized diverse broad-spectrum antiviral targets and corresponding agents from a medicinal chemistry prospective, compared the pharmacological advantages and disadvantages of different targets, listed representative agents, showed their structures, pharmacodynamics and pharmacokinetics characteristics, and conducted a critical discussion on their development potential, in the hope of providing up-to-date guidance for the development of broad-spectrum antivirals and perspectives for applications of antiviral therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)
- Published
- 2024
- Full Text
- View/download PDF
50. Expanding Complex Morpholines Using Systematic Chemical Diversity.
- Author
-
Tang SA, Fults A, Boyd SR, Gattu N, Tran KA, Fan J, MacKenzie KR, Palzkill T, Young DW, and Chamakuri S
- Subjects
- Molecular Structure, Stereoisomerism, Esters chemistry, Amino Acids chemistry, Amino Acids chemical synthesis, Chemistry, Pharmaceutical, Morpholines chemistry
- Abstract
The morpholine heterocycle is a structural unit found in many bioactive compounds and FDA-approved drugs, but the generation of more complex C-functionalized morpholine derivatives remains considerably underexplored. Using systematic chemical diversity (SCD), a concept that guides the expansion of saturated drug-like scaffolds through regiochemical and stereochemical variation, we describe the synthesis of a collection of methyl-substituted morpholine acetic acid esters starting from enantiomerically pure amino acids and amino alcohols. In total, 24 diverse substituted morpholines were produced that vary systematically in regiochemistry and stereochemistry (relative and absolute). These diverse C-substituted morpholines can be directly applied in fragment screening or incorporated as building blocks in medicinal chemistry and library synthesis.
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.