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In order to obtain potential anticancer agents, hybrid compounds have been synthesized by coupling thiazolidinone and pyrazole scaffolds. Among the synthesized compounds, 2-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl thiazolidin-4-one (4a) was found to be the most potent based on a docking (−9.307) and binding scores (−66.46), along with good ADME parameters. In vitro anticancer activity of compound 4a shows a maximum inhibition against lung cancer (NCI-H23) cell lines with a moderate inhibition rate of 31.01%. Molecular docking studies revealed that these hybrid compounds bind well to the active site of peroxisome proliferator-activated receptors-gamma (PPAR-gamma). Doxorubicin was used as a positive control. It can be concluded that 4a having pyrazole-thiazolidinone ring systems has the potential to be developed as an anticancer agent. [ABSTRACT FROM AUTHOR]

Myrica esculenta plant extracts have been reported for their anticancer properties. Also, albumin has been reported as a drug carrier due to non-immunogenic nature and ability to bypass the reticuloendothelial system (RES). In this study Myrica esculenta plant extract-based albumin nanoparticles (ME-BSANPs) were characterized and prepared for cancer therapy. The objective of this study is to enhance the absorption of the phytoconstituents and to improve cancer cell selectivity that leads to apoptosis. The prepared nanoparticles were examined for their morphological characteristics, such as, size, shape, surface charge, and stability. Furthermore, the design of expert (DOE) software was used to determine the formulation parameters. The size of the synthesized nanoparticles were analyzed and images were observed in the filed emission scanning electron microscopy (FESEM). In vitro studies of these nanoparticles were tested on cancer cell line (MIA PaCa-2) and resulted to cell cytotoxicity with an increase in the level of apoptosis or programmed cell death. The study of molecular docking was reported in Myrica esculenta bark. The docking was performed with BSA to check the binding affinity because BSA-based nanoparticles embedded with plant extract may interact with cancer targets. Docking studies revealed that the plant phytoconstituents have good binding affinity to BSA, which may carry these nanoparticles to target the cancer site to trigger apoptosis. These research findings suggest that the plant extract-loaded albumin-based nanoparticles could be a new development in cancer treatment. Also, these nanoparticles showed an excellent drug delivery and anticancer activities with fewer side effects. [Display omitted] • Myrica esculenta plant extracts demonstrated anticancer properties, making them a promising candidate for cancer therapy. • Albumin was chosen as a drug carrier because it easier for therapeutic agents to reach the right places. • The study focuses on the development and characterizing of ME BSANPs for cancer therapy, aiming to enhance the absorption of phytoconstituents selectivity, leading to apoptosis. • The nanoparticles were optimized using Design of Expert (DOE) software ensuring the effectiveness and safety of the nanoparticulate drug delivery system. • In vitro experiments using the MIA PaCa-2 cancer cell line showed cytotoxicity and increased apoptosis, highlighting the as effective anti-cancer agents. [ABSTRACT FROM AUTHOR]

In continuation to our previous studies on cyanopyrimidine derivatives as anticancer agents, we further designed, synthesized, and evaluated new 3,4,5‐trimethoxy phenyl ring pendant sulfur‐containing cyanopyrimidine derivatives (4a–m) with a particular lipophilic behavior. In this work, we have varied the chain length from isopropyl to isopentyl and evaluated their anticancer activities. To study the antiproliferative spectrum, in vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute, United States. Compound 4g (NSC: D‐813664) displayed the most promising broad‐spectrum anticancer activity with high growth inhibition of various cell lines representing action against multiple cancers diseases. It showed percentage growth inhibition of 84.01 and 76.94 against SR leukemia and HCT‐116 colon cancer cell lines. Absorption, distribution, metabolism, excretion, and toxicity studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 6‐(3,4,5‐trimethoxyphenyl) pyrimidine‐5‐carbonitrile derivatives exhibited its anticancer activity through different targets and hence could be further structurally modified and optimized to develop more potent multi‐targeting anticancer agents. [ABSTRACT FROM AUTHOR]

Abstract: A series of 6-aminomethyl-2-aryl-1-benzopyran-4-one derivatives (10–24) were synthesized. The compounds were tested for anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. Among the tested compounds, six compounds 11, 13, 16, 18, 21 and 23 showed higher degree of anti-inflammatory activity (>75% activity of standard drug ibuprofen). In addition to remarkable anti-inflammatory activity, analgesic activity was found to be comparable with that of the standard drug ibuprofen. Compounds 16 and 21 showed a significant GI protection (with respect to ulcerogenesis) and a marked decrease in lipid peroxidation values whereas compounds 11 and 16 were found to possess antimicrobial activity against Staphylococcus aureus, Escherichiacoli, Rhizopus oryza and Penicillum citrum with an MIC of 10μg/mL. [Copyright &y& Elsevier]

Graphical abstract Highlights • Novel series of Schiff base derivatives of octadec-9-enoic acid have been synthesized. • Molecular properties of metabolites were calculated using Lipinski's rule of five. • Molecular docking study was done on active site of co-crystallized structure of PPAR-γ using PDB ID1FM9. • Compounds S21, S10 and S7 exhibited most promising anti-diabetic activity. • Synthesized fatty acid derivatives can be further investigated to develop more active anti-diabetic drugs. Abstract A new series of octadec-9-enoic acid schiff base entities (S1-S30) were designed and synthesized targeting peroxisome proliferator activated receptor-gamma for agonist action. Molinspiration software (online) was used to estimate drug like molecular properties of the metabolites. Docking disquisition on co-crystallized protein of PPAR-γ (PDB ID 1FM9) was carried out which showed S21 , S10 and S7 as best situated in the vital sites of receptor having docking scores −9.19, −8.68 and −8.64 respectively. Free binding energy measured using model of Maestro 9.0 and was in range of from −40.01 and −80.54 kcal/mol, significant when compared with pioglitazone (−51.58 Kcal/mol). Seven best docked derivatives were assessed for in-vivo oral glucose tolerance on normal rats and anti-hyperglycaemic activity by streptozotocin induced diabetes model. S21 unveiled to be the best measured analogue among all the synthesized entities. Encouraging outcomes motivates fatty acids for further development of more effective and safer compounds. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Synthesis of new hybrid analogues incorporating benzothiazole, oxadiazole, 4-thiazolidinone. • ADME analysis; all compounds follow the Rule of Five. • Molecular docking study performed on PPAR-γ. • In-vivo anti-diabetic screening by OGTT and STZ model. • Three compounds Tz21, Tz17, Tz10 appeared as most potent anti-diabetic agents. Abstract A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15 ± 1.79 mg/dL, 154.39 ± 1.71 mg/dL, 167.36 ± 2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32 ± 1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ± 0.01 µM, 9.03 ± 0.12 µM and 11.96 ± 0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ± 0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally. [ABSTRACT FROM AUTHOR]

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF- α target. Among all the docked molecules, compound 3f showed best glide score of −6.89. All the synthesized compounds were evaluated for in vivo anti-inflammatory activity by carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX-2 and NF- κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver. [ABSTRACT FROM AUTHOR]

Nineteen novel piperine based triazoles have been synthesized using click chemistry approach and were tested for in vivo anti-inflammatory activity. The most active compounds were evaluated for in vitro TNF-α expression. Compounds 3g and 3f were found to show significant in vivo inhibition of inflammation, 80.40% and 76.71% , respectively after 5 h in comparison to piperine ( 54.72 %) and the standard drug indomethacin ( 77.02 %) without causing any damage to the stomach. Compounds 3g and 3f suppressed TNF-α level by 73.73% and 70.64% , respectively and protein expression of COX-2, NF–κB and TNF-α more than indomethacin. Moreover, the compound 3g was found to show significant analgesic activity of 54.09% which was comparable with the indomethacin ( 57.43% ). [ABSTRACT FROM AUTHOR]

• Alginic acid, a natural carbohydrate is explored as a green bifunctional heterogeneous, biopolymeric organocatalyst for the expeditious synthesis of dihydropyrimidines (DHPMs). • A mild reaction protocol with high to quantitative yields (82–96%). • The catalyst was characterized through X-ray diffraction, thermogravimetric analysis, scanning electron microscopy and infrared spectroscopic techniques. • Reusability of the catalyst was assessed up to five consecutive cycles. Cancer remains considered as one of the leading global health problems either due to meagre and suboptimal therapeutic response of chemotherapeutic agents or due to the emergence of spontaneous complex multidrug resistance in cancer cells. This created a persistent need for the development of new anticancer agents. Enthralled by the high success rate for natural product-based drug discovery and current research scenario, we synthesized a new series of 3,4,5-trimethoxy phenyl ring pendant sulfur‐containing cyanopyrimidine derivatives clubbed with different amines intending to search an anticancer lead compound. To probe the anti-proliferative spectrum of the synthesized derivatives, an in-vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute (NCI) representing major types of cancer diseases. Most of the derivatives showed good to moderate anti-proliferative activity. The results revealed that compound 4e displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing multiple cancers diseases. Mechanistic investigation of compound 4e in human breast cancer MDA-MB-231 cells showed that compound 4e triggers cell death through the induction of apoptosis. ADMET studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 3,4,5-trimethoxy phenyl ring pendant sulfur‐containing cyanopyrimidine derivative 4e could act as a promising hit molecule for further development of novel anticancer therapeutics. [ABSTRACT FROM AUTHOR]

The triptans class of pharmaceuticals, which was created to treat acute migraine, is made up of indole-containing drugs that bind to a subset (1B/1D) of 5-hydroxytryptamine receptors and are agonists of serotonin receptors. At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists. Zolmitriptan, a synthetic tryptamine derivative and a well-known member of the triptan family, is available as an orally disintegrating tablet, nasal spray, and tablet. There are melt formulations of rizatriptan and zolmitriptan available on the market that are easier to use and absorb, comparable to regular pills. Recently, the FDA approved zolmitriptan, a medication with tolerability comparable to sumatriptan. Whereas zolmitriptan is only available as an oral melt or tablet, sumatriptan is available as a nasal spray, oral preparation, or self-injectable kit. The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine. However, zolmitriptan binds to plasma proteins only 25% of the time because of significant first-pass degradation. Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Cancer has become a major concern in healthcare globally, and over time, incidences and prevalence of cancer are increasing. To counter this, a lot of anticancer drugs are approved and are in clinical use, playing a pivotal role in its treatment. Due to drug resistance and adverse effects, a continuous demand for novel, potent, and safe candidates to treat cancer is always there. Over the last few decades, various heterocyclic ring-based derivatives have been explored and reported in the literature. In this regard, benzothiazole scaffold-based compound emerged as the versatile ring for developing novel and safe anticancer candidates. In this article, we have reported various benzothiazole heterocyclic ring-based derivatives demonstrating potent antiproliferative activity by induction of apoptosis via an intrinsic pathway in a dose-dependent manner. These compounds also displayed inhibition of different enzymes, for example, Aurora kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, phosphoinositide kinases, DNA topoisomerase, and tubulin polymerases. This study focused on a comprehensive overview of antiproliferative activity, structure-activity relationship, apoptosis induction activity, and enzyme inhibition by benzothiazole-based compounds., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

In order to determine whether thiazolobenzamide molecules connected to naphthalene could inhibit the growth of three different tumor cell lines, MCF7 (breast carcinoma), A549 (pulmonary carcinoma), and DU145 (prostatic adenocarcinoma) a novel series of ten molecules, designated TA 1-10, was designed, synthesized, and tested. Among these compounds, TA7 showed promising results against cell lines, especially showing exceptional efficacy against breast cancer. Antioxidant activity tests consistently showed the best performance from the TA7 molecule. Furthermore, when a dose of 50 to 500 mg/kg of the total mass of rats is given, the most effective chemical, TA7, did not exhibit any harmful effects during acute oral toxicity tests. The biochemical indicators (SGOT and SGPT) for hepatotoxicity associated with compound TA7 were found to be fairly similar to those of the control group. The findings from molecular docking, XP visualization, and MM-GBSA dG binding investigations are in agreement with the outcomes of in-vitro tests of antioxidant and anticancer capabilities. TA7 was the most effective compound among those that were docked; it bound free energy and had adequate properties for metabolism (biochemical processes), distribution (dispersion), absorption (assimilation), and excretion (elimination). This study found that the TA7 molecule, a thiazole ring system derivative connected to naphthalene, is to be a promising and possible anticancer agent and its efficacy may be further explored in clinical studies., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors., Aims: We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately., Methods: Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies., Results: The ADME profile of synthesized compounds was found to be satisfactory., Conclusion: The synthesized compounds can serve as lead for further drug designing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This article emphasizes the importance of prodrugs and their diverse spectrum of effects in the field of developing novel drugs for a variety of biological applications. Prodrugs are chemicals that are supplied inactively, but then go through enzymatic and chemical transformation in vivo to release the active parent medication that can have the desired pharmacological effect. By adding an inactive chemical moiety, prodrugs are improved in a number of ways that contribute to their potency and durability. For the purpose of illustrating the usefulness of the prodrug approach, this review covers examples of prodrugs that have been made available or are now undergoing human trials. Additionally, it included lists of the most common functional groups, carrier linkers, and reactive chemicals that can be used to create prodrugs. The current study also provides a brief introduction, several chemical methods and modifications for creating prodrugs and mutual prodrugs, as well as an explanation of recent advancements and difficulties in the field of prodrug design. The primary chemical carriers employed in the creation of prodrugs, such as esters, amides, imides, NH-acidic carriers, amines, alcohols, carbonyl, carboxylic, and azo-linkages, are also discussed. This review also discusses glycosidic and triglyceride mutually activated prodrugs, which aim to deliver the drugs after bioconversion at the intended site of action. The article also discusses the extensive chemistry and wide variety of applications of recently approved prodrugs, such as antibacterial, anti-inflammatory, cardiovascular, antiplatelet, antihypertensive, atherosclerotic, antiviral, etc. In order to illustrate the prodrug and mutual drug concept's various applications and highlight its many triumphs in overcoming the formulation and delivery of problematic pharmaceuticals, this work represents a thorough guide that includes the synthetic moiety for the reader., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

With an increase in the progression of research and development in the medical field, the experimental use of animals for the efficacy and safety testing of pharmaceuticals is on rise. Every year, millions of animals are used for experimental testing during which these suffer from pain and are then eventually sacrificed. Besides bioethical issues, animal experimentation is associated with many disadvantages like high cost, the requirement of skilled manpower, approval, and is time-consuming. Therefore, attempts have been made by researchers to design and develop a number of alternative methods that could bypass animal experiments. These methods not only give accurate results but can also save lives of millions of animals annually. Research techniques, including computer and robotics together with molecular biology techniques, are applied to discover new methods to replace animal testing. Several alternative methods are discussed in this review. Some of these methods can predict the behavior of drugs accurately and are as reliable as in-vivo animal models. Furthermore, these alternative methods offer a variety of advantages over experimental animals. However, there is still a great need to discover and develop new, accurate, and reliable methods to replace experimental animals., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Durable concrete significantly reduces the spalling caused by chemical damage. The objective of current research is to substitute cement with supplementary such as fly ash (FA), ground granulated blast furnace slag (GGBS), and alccofine (AF). Additionally, the impact of nano-silica (NS) and silica fumes (SF) on the GPC durability when cured at various temperatures has been attempted. In order to perform this, GPC samples were produced by combining NS and SF at proportions of 0.5% NS + 5% SF, 1% NS + 10% SF, and 1.5% NS + 15% SF, and then cured at temperatures of 27 °C, 60 °C, 90 °C, and 120 °C, respectively. In this research, all concrete specimens were continuously immersed for twelve weeks under four different chemicals, i.e., HCl (2%), H 2 SO 4 (2%), NaCl (6%), and Na 2 SO 4 (6%). The influence of chemical attack on the qualities of concrete was examined by evaluating the water absorption, sorptivity, loss of mass, and loss of GPC strength. The durability aspect is also studied by visual appearance and mass loss under harmful chemical attack. The combination of GPC with integrated NS and SF affords great resistance against chemical attacks. The percentages of these two components are 1.5% and 15%. For GPC specimens, when cured at 90 °C, the resultant strength is found at its maximum.

Cancer is one of the severe diseases in which abnormal cells divide and proliferate in an uncontrolled manner without any regulation. Globally cancer is among the leading causes of death; according to a recent report of by the WHO, around 10 million people died in 2018 due to cancer. It has also been reported that by 2040, approximately 30 million new cases will be reported every year. The increase in the incidences of cancer is taking a toll on the health care system worldwide. Considerable scientific literature is available on anticancer agents but newer therapeutic strategies are still required in this field to address novel approaches to drug design and discovery to counter this problem. Imidazothiazole represents a privileged scaffold in medicinal chemistry and provides the medicinal chemist the possibility to modulate the physiochemical properties of the lead compound. In recent times, imidazothiazole scaffold is broadly explored for its anticancer activity, which acts through various mechanisms such as EGFR, B-RAF, DHFR kinase inhibition and tubulin polymerization inhibition and other molecular mechanisms of action. Due to their feasible synthetic accessibility and promising pharmacological profile, it has attracted various medicinal chemists to explore and develop imidazothiazole derivatives as potent and safe anticancer agents. In the present article, we have reviewed various potent imidazothiazole scaffold-based derivatives reported as anticancer agents, their synthetic strategies, Structure Activity Relationship (SAR), mechanism of action, and molecular docking along with their future perspective. This review will be very useful for medicinal chemists for drug design and development of imidazothiazole-based potent antiproliferative agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Anthocyanins are naturally occurring water-soluble flavonoids abundantly present in fruits and vegetables. They are polymethoxyderivatives of 2-phenyl-benzopyrylium or flavylium salts. Delphinidin (Dp) is a purple-colored plant pigment, which occurs in a variety of berries, eggplant, roselle, and wine. It is found in a variety of glycosidic forms ranging from glucoside to arabinoside. Dp is highly active in its aglycone form, but the presence of a sugar moiety is vital for its bioavailability. Several animal and human clinical studies have shown that it exerts beneficial effects on gut microbiota. Dp exhibits a variety of useful biological activities by distinct and complex mechanisms. This manuscript highlights the basic characteristics, chemistry, biosynthesis, stability profiling, chemical synthesis, physicochemical parameters along with various analytical methods developed for extraction, isolation and characterization, diverse biological activities and granted patents to this lead anthocyanin molecule, Dp. This review aims to open pathways for further exploration and research investigation on the true potential of the naturally occurring purple pigment (Dp) in its anthocyanidin and anthocyanin forms beyond nutrition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Husain, Chanana, Khan, Dhanalekshmi, Ali, Alghamdi and Ahmad.)

Background: Malaria parasite strains are resistant to the therapeutic effect of prophylactics medicines presently available. This resistance now poses a significant challenge to researchers to beat malaria parasitic infections. Strategies such as investigating newer hybrid chemical entities and specified drug targets may help us spot new efficient derivatives that bind to the parasites in a more specific manner and inhibit their growth., Objective: To scientifically perform the experimental, pharmacological, and computational studies of pyrazole-based furanone hybrids as novel antimalarial agents., Methods: A series of new furanone-based pyrazole derivatives were synthesized and investigated as potential antimalarial agents by performing in vitro antimalarial activity. To get further optimization, these synthesized derivatives were virtually screened based on ADME-T filters, and molecular docking studies were also accomplished on the crystal structures of Plasmodium falciparum lactate dehydrogenase (PfLDH). Furthermore, the in-silico prediction was supported by performing an LDH assay., Results: The docking data suggested that the designed hybrid of furanone-pyrazole may act as PfLDH inhibitors. It was found that the results of experimental in vitro antimalarial activity and in silico analysis correlate well to each other to a good extent. The compounds (7d), (7g), and (8e) were found to be the most potent derivatives with IC 50 values of 1.968, 1.983, and 2.069 μg/ml, respectively., Conclusion: From the results, it may be concluded that compounds that are active in low doses might be adopted as a lead compound for the development of more active antimalarial agents. The synthesized compounds (7d), (7g), and (8e) exhibited good antimalarial activity with PfLDH inhibition. The best compounds can be explored further in the future for designing the potent inhibitors of PfLDH as new potent antimalarial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Indoline-2,3-dione comprises a leading course group of heterocycles endowed with appealing biological actions, including anticancer activity. There are significant justifications for exploring the anticancer activity of Schiff base derivatives of isatin as a vast number of reports have documented remarkable antiproliferative action of isatin nucleus against various cancer cell lines., Aims and Objectives: A series of arylthiazole linked 2H-indol-2-one derivatives (5a-t) was designed and synthesized as potential VEGFR-2 kinase inhibitors keeping the essential pharmacophoric features of standard drugs, like sunitinib, sorafenib, nintedanib, etc. They were evaluated for their in vitro anticancer activity. The aim of this study was to investigate and assess the anticancer potential of isatin-containing compounds along with their kinase inhibition activity., Methods: The title compounds were synthesized by reacting substituted isatins with para-substituted arylthiazoles using appropriate reaction conditions. Selected synthesized derivatives went under preliminary screening against a panel of 60 cancer cell lines at NCI, the USA, for single-dose and five dose assays. Molecular docking was performed to explore the binding and interactions with the active sites of the VEGFR-2 receptor (PDB Id: 3VHE). Derivatives 5a, 5b, 5c, 5d, 5g, 5h, and 5m were assessed for in vitro inhibition potency against Human VEGFR-2 using ELISA (Enzyme- Linked Immunosorbent Assay) kit. All the target compounds were determined against human colon cancer cell line SW480 (colorectal adenocarcinoma cells). Cellular apoptosis/necrosis was determined by flow cytometry using annexin V-FITC. DNA content of the cells was analyzed by flow cytometry and the cycle distribution was quantified., Results: Compounds 5a and 5g exhibited noteworthy inhibition during a five-dose assay against a panel of 60 cell lines with MID GI 50 values of 1.69 and 1.54 μM, respectively. Also, both the lead compounds 5a and 5g demonstrated promising VEGFR-2 inhibitory activity with IC 50 values of 5.43±0.95 and 9.63±1.32 μM, respectively. The aforesaid potent compounds were found effective against SW480 (colorectal adenocarcinoma cells) with IC 50 values of 31.44 μM and 106.91 μM, respectively. Compound 5a was found to arrest the cell cycle at the G 2 /M phase, increasing apoptotic cell death. The docking study also supported VEGFR-2 inhibitory activity as both compounds 5a and 5g displayed promising binding and interactions with the active sites of VEGFR-2 receptor (PDB: 3VHE) with docking scores - 9.355 and -7.758, respectively. All the compounds obeyed Lipinski's rule of five., Conclusion: Indoline-2,3-dione and thiazole have huge potential to be considered a steer combination approach for developing promising kinase inhibitors as cancer therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Benzothiazole is an organosulfur heterocyclic compound that has a considerable place in drug discovery due to significant pharmacological actions., Objective: The main objective of the present study was to synthesize some novel 2-(5-substituted 1,3,4-oxadiazole-2-yl)-1,3-benzothiazole derivatives and evaluate them for their anticonvulsant activity using in silico and in vivo methods., Methods: A set of sixteen 2-(5-substituted 1, 3, 4-oxadiazole-2-yl)-1, 3-benzothiazole derivatives were prepared using multi-step reactions starting from o-amino-thiophenol and characterized by suitable spectral techniques. The synthesized compounds were evaluated for anticonvulsant activity using in silico and in vivo methods. In silico molecular docking study was performed using Molegro Virtual Docker software to analyze binding modes of compounds with the internal ligand of PDB ID: 1OHY and 1OHV; and in vivo pharmacological activities were tested for both generalized tonic-clonic seizures and generalized absence (petit mal) seizures using Maximal Electrical Shock and PTZ-induced seizure models, respectively., Results: Some new 2-(5-substituted-1,3,4-oxadiazole-2-yl)-1,3- benzothiazole (5a-5p) were successfully synthesized by finally refluxing 1, 3-benzothiazole-2-carboxyhydrazide with different aromatic acids in phosphoryl chloride. Docking results showed that compounds 5c, 5j, and 5m were found to have the highest number of H-bond interactions; i.e. 4, 4, and 7 respectively with target proteins 1OHY and 6, 3, and 4 respectively with target protein 1OHV, whereas phenytoin showed only two H-bonding with both proteins. In the Maximal electroshock seizure method, the synthesized compounds 5h, 5k and 5o demonstrated potent anticonvulsant activity against the tonic seizure with a significant decrease in tonic hind leg extension period with a mean duration of 7.9, 7.4, and 7.0 sec respectively, as compared to the other synthesized compounds. In contrast, in the PTZ-induced seizure model, compounds 5c, 5h, and 5m showed protection against clonic convulsion with significant elevation in the onset time of clonic convulsion at 311.2, 308.0, and 333.11 sec, respectively., Conclusion: Thus, from the results, it can be concluded that compound 5h, a benzothiazole derivative endowed with an oxadiazole ring, can be developed as a potential anticonvulsant agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the present study, authors want to encourage the research exertions through structureactivity relationship for the identification of effective molecules for the treatment of Human immunodeficiency virus because nowadays AIDS is considered as one of the main causes of death in human beings. A diversity of biological resources has been searched and developed for the treatment of HIV but unfortunately, until now, no medicine is found to be fully effective and safe for the cure of patients. Human immunodeficiency virus is a type of lentivirus which causes the infection of HIV and once it enters the human body, it stays for a longer period of time triggering immunodeficiency syndrome. For searching and developing new potent and effective anti-HIV molecules, medicinal chemists have engaged in countless targets with the structure-activity relationship (SAR) of molecules and on this basis, many antiretroviral therapies have been developed to cure HIV infection. Most of these new searched molecules have been found to be clinically active against various types of AIDS patient and auxiliary research in this area may lead to better treatment in the near future. This article encompasses and highlights the recent advancement of innumerable inhibitors laterally through synthetic, semi-synthetic and structure-activity relationship approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused fivemembered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their invitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, two series of imidazopyridine-linked thiazolidinone rings (5a-h and 6a-h) constituting 16 new compounds were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines, that is, MCF-7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Three compounds, 5h, 6f, and 6h, exhibited remarkable results against all three cell lines, but compound 6h was found to be the most active one against the breast cancer cell line. Among all the synthesized compounds, 6h displayed the highest antioxidant results. Furthermore, the potent compounds 5h, 6f, and 6h showed no signs of toxicity at doses ranging from 50 to 500 mg/kg of animal body weight. The biochemical parameters (SGOT and SGPT) of compound 6h nearly matched the control in hepatotoxicity studies. The molecular docking and MM-GBSADG binding studies are in agreement with the in vitro anticancer and antioxidant activity results. The most promising compound 6h was found to have the highest docking score and binding energy, and its absorption, distribution, metabolism, and excretion (ADME) parameters are in the acceptable range. Thus, it can be concluded that 6h, an imidazopyridine derivative endowed with a thiazolidinone ring system, has the potential to be developed as an anticancer agent., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

Furanone, a five-membered heteroaromatic ring containing oxygen atom, is of immense pharmaceutical importance. Presence of this nucleus in biologically active compounds of natural and synthetic origin has made it an indispensable motif for design and development of new therapeutic agents. In recent years synthesis of furanone derivatives and exploring their therapeutic actions has been the prime interest amongst researchers. Furanone containing compounds cover numerous therapeutic categories viz. Analgesic and anti-inflammatory, anticancer, anticonvulsant, antibacterial and antifungal, antioxidant, antiulcer and anti-TB, etc. There is a need to couple recent work done with previously available information on furanone, a well acknowledged scaffold, to help scientists to develop novel and new furanone based therapeutic agents at a faster pace. This updated review highlights the worth of numerous therapeutically active furanone based compounds developed by the medicinal chemists. SAR studies have also been derived which may be useful for rational designing of furanone derivatives with improved therapeutic index., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Furanone and pyrrolone heterocyclic ring system represent important and interesting classes of bioactive compounds. Medicinal chemists use these heterocycyclic moieties as scaffolds in drug design and discovery., Methods: A series of 3-arylidene-5-(naphthalene-2-yl)-furan-2(3H)-ones (2a-j) were synthesized by incorporating pharmacophore of COX-2 inhibitor rofecoxib and naphthyl ring of naproxen as potential non steroidal anti-inflammatory agents. These furanone derivatives were subsequently reacted with dry ammonia gas and benzylamine to furnish corresponding 3-arylidene-5-(naphthlen-2-yl)-1H-pyrrol-2(3H)-ones (3a-e) and 3-arylidene-1-benzyl-5- (naphthalene-2-yl)-1H-pyrrol-2(3H)-ones (4a-e), respectively. The newly prepared heterocyclics were screened for their expected in-vivo biological activities including anti-inflammatory, analgesic and ulcerogenic actions in rodents. The COX-2 inhibitory behavior of synthesized compounds was also assessed via automated docking studies., Results: The chemical structure of the synthesized compounds was characterized by using modern spectroscopic techniques. Result of in-vivo pharmacological studies demonstrated that almost all N-Benzyl-pyrrol-2(3H)-ones (4a-e) showed better anti-inflammatory and analgesic activities in comparison with the other two series of furan-2(3H)-ones and pyrrol- 2(3H)-ones. The moldock score value of the tested compounds was found in the range of -116.66 to -170.328 and was better than the standard drug., Conclusion: Among all the synthesized compounds, only nine compounds (2d, 2g, 2h, 3d, 4a, 4b, 4c, 4d and 4e) exhibited potent anti-inflammatory and analgesic activities with significantly reduced gastrointestinal toxicity in various animal models in comparison to standard drug, diclofenac. Therefore, it is recommended to explore the potential of the synthesized compounds as lead candidates for the development of new therapeutic agents.

A series of pyrazolo[3,4-b]quinolines have been synthesized using one-pot water mediated synthetic route under microwave irradiation involving the condensation of 2-chloroquinoline-3-carbaldehydes with semicarbazide or 2,4-dinitrophenyl hydrazine. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. The pharmacological evaluation showed that the compounds are good at inhibiting edema induced by carrageenan and also showed prominent analgesic activity with lesser GI toxicity as indicated by severity index and LPO values.

A series of bis-chalcones (3a-g) and their flavones derivatives (4a-g) were synthesized and evaluated for their antimicrobial activity. Bis-chalcones were prepared by condensing 1,1'-(4,6-dihydroxy-1,3-phenylene)diethanone (2) with appropriate aryl aldehydes following Claisen-Schmidt reaction conditions. Oxidative cyclization of bis-chalcones (3a-g) in DMSO in the presence of iodine furnished flavones (4a-g). The synthesized compounds were evaluated for their antibacterial and antifungal actions against some selected microbes. The results of antimicrobial evaluation showed that some of the synthesized compounds were good in their antibacterial and antifungal actions.

Thirteen new 6-(1-H-indole-2-yl)-4-oxo-2-[2-(substituted-benzylidene)-hydrazinyl]-4,5-dihydropy-rimidine-5-carbonitrile derivatives were synthesized. The title compounds, hydrazones, were synthesized by reaction of hydrazine group of 2-hydrazinyl-4-(1-H-indole-2-yl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile (2) with different substituted aromatic aldehydes using a mixture (2:8, v/v) of glacial acetic acid and alcohol. The required intermediate compound 2 was synthesized from 2-mercapto-4-(1-H-indole-2-yl)-6-oxo-1,6-dihy-dropyrimidine-5-carbonitrile 1 upon nucleophilic attack by the hydrazine hydrate. Compound 1 was synthesized by modified Biginelli condensation method using indole-3-carbaldehyde, ethyl cyanoacetate and thiourea. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and antimicrobial actions. Among the newer derivatives, one compound i.e., 6-(1-H-indole-2-yl)-4-oxo-2-[2-(2,6-dichlorobenzylidene)-hydrazinyl]-4,5-dihydropyrimidine-5-carbonitrile (7) emerged as lead compound having 71.14% inhibition of edema and 12.5 microg/mL MIC against both bacterial and fungal strains.

A series of 1,2,4-trisubstituted-1H- imidazole derivatives (4a-o) was synthesized by reacting 2,4-disubstituted-1H-imidazoles (3a-o) with chlorobenzene in the presence of triethylamine. Phenylglyoxal (2) was reacted with different aromatic aldehydes in the presence of ammonium acetate and glacial acetic acid to afford the disubstituted imidazoles (3a-o). The structures of the synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results. Anticonvulsant activity was shown by majority of the synthesized compounds in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens when given i.p. to mice. In anticonvulsant screening, only one compound 4k showed potent activity comparable to that of standard drugs phenytoin and carbamazepine. Compounds 4a, 4c, 4e, 41 and 4n passed the rotorod test successfully without any sign of neurological deficit.

A series of 2-(substituted-phenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazoles (3-15) were synthesized. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. The percentage inhibition in edema at different time intervals indicated that compounds 8, 11, 12, 14 and 15 exhibited good anti-inflammatory potential. The results illustrate that 2-(2-acetoxyphenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazole (15) and 2-(3,4-dimethoxyphenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazole (12) showed best anti-inflammatory activity among the series tested. Furthermore, activity is higher in case of chloro substitution as compared to methyl substitution. The compounds synthesized were also evaluated for their ulcerogenic and lipid peroxidation action and showed superior GI safety profile along with reduction in lipid peroxidation as compared to that of ibuprofen.

A series of substituted 3-[(substituted-2-chloroquinolin-3-yl)methylene]-5-(substituted-phenyl)-furan-2(3H)-ones (4a-p) have been synthesized and evaluated for their in vitro antimalarial activity against P. falciparum. The title compounds were synthesized by condensing 3-(substituted-benzoyl)propionic acids (3a-d) with substituted 2-chloroquinoline-3-carbaldehydes (2a-d) following modified Perkin's reaction. Compounds 3-[2-chloro-6-methylquinolin-3-yl)methylene]-5-(2,4-dimethyl-phenyl)-furan-2(3H)-one (4n) and 3-[2-chloro-6-methoxyquinolin-3-yl)methylene]-5-(2,4-dimethyl-phenyl)-furan-2(3H)-one (4p) showed promising antimalarial activity with MIC of 10 microg/mL.

In the present study, a series of Mannich bases was synthesized by condensing 4,6-diacetylresorcinol with formaldehyde and some selected secondary amines following the Mannich reaction conditions. Findings revealed that Mannich reaction did not take place at the acetyl function but occurred on the aromatic ring position between the two hydroxyl groups. It was also observed that in one case instead of the desired base (3a), the dimer (4) of the starting material (4,6-diacetylresorcinol) having a methylene bridge could be isolated. The newly synthesized compounds were characterized on the basis of elemental analysis as well as 1H NMR and mass spectral data. The products have been evaluated for antiinflammatory, ulcerogenic and lipid peroxidation actions with some significant results.

In the present study, various amide derivatives of sulfanilamide, sulfamethoxazole, sulfadiazine, dapsone and isoniazid have been synthesized by condensing them with appropriate 4-oxo-4-(4-substituted phenyl)butanoic acid moiety. The compounds have been evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Their structures were established on the basis of elemental analysis, 1H NMR and mass spectral data. Some of the compounds were found to have significant antiinflammatory and antibacterial activities. Additionally, these derivatives were low in their ulcerogenic action, which is the main side effect of commonly used NSAIDs.

Synthesis and biological evaluation of various aroylpropionic acid derivatives containing 1,3,4-Oxadiazole nucleus is reported here. The compounds (3a-w) were synthesized by cyclization of 3-aroylpropionic acids into 1,3,4-oxadiazole nucleus by treating with various aryl acid hydrazides in the presence of POCl(3). The structures of new compounds are supported by IR, (1)H NMR and MS data. These compounds were tested in vivo for their anti-inflammatory activity. All the compounds tested showed anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. Seven (3c, g, i, j, m, o, p) out of 23 new compounds showed very good anti-inflammatory activity in the carrageenan-induced rat paw edema test with very less ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA), which is one of the byproducts of lipid peroxidation. Compound 3i and o showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid induced writhings and 0.7 and 0.65 of severity index respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen. The study showed that the cyclization of carboxylic group of aroylpropionic acids into an oxadiazole nucleus resulted in compounds having good anti-inflammatory and analgesic effects with reduced gastric irritation.

Disubstituted imidazoles were prepared by reacting appropriate phenylglyoxal with different aryl aldehydes in the presence of ammonium acetate. Trisubstituted imidazoles were prepared by reacting disubstituted imidazoles with chlorobenzene in the presence of catalytic amount of triethylamine (TEA). The synthesized compounds were characterized on the basis of IR, 1H-NMR and mass spectral data and elemental analysis results. They were tested for their antiinflammatory and antimicrobial actions. Two compounds showed good antiinflammatory activity in carrageenan induced rat paw edema test with very low ulcerogenic activity. Fair number of compounds were found to have significant antimicrobial activity especially against fungal species.

In the present investigation, a series of 3,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives (6a-t) were synthesized and evaluated for their anticonvulsant activity and neurotoxicity. The structures of synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results. In anti-MES activity compounds 6b, 6c, 6g, 6j, 6k, 6q and 6r showed potent activity comparable to that of standard drugs: phenytoin and carbamazepine. Compounds 6c, 6k, 6n, 6p and 6s successfully passed the rotorod test without any sign of neurological deficit.

A series of 3-arylidene-5-(substituted phenyl)-2(3H)-furanones (3-10) and their nitrogen analogues, 3-arylidene-5-(substituted phenyl)-1-benzyl-2(3H)-pyrrolone (11-14), and 3-arylidene-5-(substituted phenyl)-2(3H)-pyrrolones (15-21) were synthesized. All the compounds were screened for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv (ATCC 27294) in BACTEC medium using the Microplate Alamar Blue Assay (MABA). Among the synthesized compounds, compound 19, 3-(4-chlorobenzylidene)-5-(4-methylphenyl)-2(3H)-pyrrolone, emerged as a lead compound having the highest activity against Mycobacterium tuberculosis. The antimycobacterial activity was found to improve upon replacement of oxygen of furanone ring with nitrogen atom (pyrrolones), however, substitution with benzylamine moiety (1-benzylpyrrolones) markedly decreases the activity.

In the present investigation, two novel series of 2-[3-(4-chlorophenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazole and 2-[3-(4-ethylphenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazole were synthesized and tested for their antiinflammatory, analgesic, ulcerogenic and antibacterial actions. A fair number of compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a few compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action and moderate antibacterial action.

A series of amino-5-[(substituted) phenyl]-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H- 1-pyrazolylmethanethione were synthesized by the reaction between thiosemicarbazide and chalcones and were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv and INH resistant Mycobacterium tuberculosis using bactec method. Among the synthesized compounds, compound (4b), amino-5-(4-chlorophenyl)-3-(4-hydroxy-3-methylphenyl)-4, 5-dihydro-H-1-pyrazolylmethanethione was found to be the most active agent against Mycobacterium tuberculosis H37Rv (MTB) and INH resistant Mycobacterium tuberculosis (INHR-MTB) with minimum inhibitory concentration of 0.43 microM . When compared to INH-compound (4b) was found to be 1.62 fold and 26.41 fold more active against MTB and INHR-MTB, respectively.

Unlabelled: Glycogen storage disease (GSD)-1b has been associated with neutropenia and abnormalities of neutrophil function. Many individuals with GSD-1b manifest chronic gastrointestinal inflammation. Our study was performed to precisely establish the type, frequency, and spectrum of gastrointestinal disease in patients with GSD-lb. We established a medical database of 36 individuals affected with GSD-1b, utilizing patients at our center, disease registries, and direct contacts with North American referral centers specializing in genetic disorders. Records were reviewed, focusing on documentation of gastrointestinal involvement. Gastrointestinal symptoms or manifestations were present in approximately 75% of the patients, including chronic abdominal pain and diarrhea, perianal fistula or abscess, and oral aphthous ulceration. Of patients identified, 28% had documented inflammatory bowel disease (IBD) and an additional 22% of patients had symptoms highly suggestive of IBD, but had not undergone comprehensive diagnostic evaluation. Gastrointestinal involvement was found to be indistinguishable from idiopathic Crohn disease (CD) by detailed review of clinical, radiologic, endoscopic and histopathologic findings. Many patients had significant improvement or resolution of gastrointestinal disease in response to G-CSF treatment. The expression of CD in patients with GSD-1b may be delayed or prevented by G-CSF treatment., Conclusion: a strong association exists between glycogen storage disease type 1b and inflammatory bowel disease. A high index of suspicion for Crohn disease should be applied in evaluating patients with glycogen storage disease type 1b and intestinal symptoms. These results provide further support for the hypothesis that some forms of inflammatory bowel disease may result from impaired mucosal innate immunity. Additional investigations into the intestinal disease in glycogen storage disease type 1b may be directly relevant to the etiology and treatment of idiopathic Crohn disease.