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Tyrosinase is an enzyme crucial for the progression of melanogenesis. Immoderate production of melanin may be the cause of hyperpigmentation and darkening leading to skin diseases. Tyrosinase is the most researched target for suppressing melanogenesis since it catalyzes the rate-limiting stage of melanin production. Thiosemicarbazones have been reported to possess strong inhibition capability against tyrosinase. We have designed and synthesized eighteen N-tosyl substituted indole-based thiosemicarbazones as competitive tyrosinase inhibitors in the current work. All the compounds exhibited outstanding to good potency with half maximal inhibitory concentration in the range of 6.40 ± 0.21 µM to 61.84 ± 1.47 µM. The compound 5r displayed the top-tier inhibition amongst the entire series with IC 50  = 6.40 ± 0.21 µM. Compounds, 5q and 5r exhibited competitive inhibitions in concentration dependent manner with Ki = 3.42 ± 0.03 and 10.25 ± 0.08 µM respectively. The binding mode of 5r was evaluated through in silico molecular dynamics simulations and molecular docking, while ADME assessment studies predicted the drug-like characteristics of the derivatives. The newly synthesized derivatives may serve as a structural guide for designing and developing novel tyrosinase inhibitors., (© 2024. The Author(s).)

Catechol- O -methyltransferase (COMT) inhibitors have played a crucial role in the development of potent and selective drugs for the treatment of Parkinson's disease, depression, and anxiety disorders. This review provides a comprehensive analysis of the structure-activity relationship (SAR) of COMT inhibitors, highlighting key structural features and pharmacophoric elements that govern their potency, selectivity, and pharmacokinetic properties. This review also discusses the application of SAR principles in the design and optimization of COMT inhibitors. Our analysis reveals the emergence of novel chemical scaffolds and the potential for COMT inhibitors to address unmet medical needs in neurology and psychiatry. This Perspective serves as a valuable resource for clinicians and researchers, providing insights into the rational design of COMT inhibitors and the development of next-generation therapeutics., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential., Method: This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 μM. The derivative 5h, with an IC50 of 13.60 ± 2.51 μM, emerged as the most potent inhibitor., Results: Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of -6.30 Kcal/- mol, consistent with experimental results., Conclusion: All findings underscored the potential of synthesized derivatives for drug development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Monitoring of food freshness is considered one of the crucial challenges for both customers/consumers and the food industries. In this study, we developed a curcumin-based starch film (F1) for pH-sensitive intelligent food packaging application. The starch was obtained from waste seeds of Artocarpus lakoocha (NS-MJF). The native starch underwent various physical and chemical modifications to yield modified starches (S1 [Autoclave heat treated], S2 [osmotic-pressure treated], S3 [citric acid treated]). The native starch was then used further for the formation of curcumin (2.5 % w/w)-based film (F1). We had analyzed these starches for solubility, colour analysis, biodegradability, oil absorption capacity, and moisture content, etc. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed favourable microstructures. The addition of curcumin to the starch enhanced the contact angle and elongation at the break of the resulting films. Antioxidant and antimicrobial assays, along with real-time freshness monitoring of chicken fillets, were also conducted. Thus, our findings may contribute to the optimization of pH-responsive biopolymer-based films for intelligent poultry packaging, promising advancements in food preservation and safety., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors. The current study seeks to contribute to the identification of efficacious POP inhibitors through the design, synthesis, and comprehensive evaluation (both in vitro and in silico) of thiazolyl thiourea derivatives (5a-r). In vitro experimentation exhibited that the compounds displayed significant higher potency as POP inhibitors. Compound 5e demonstrated an IC 50 value of 16.47 ± 0.54 μM, representing a remarkable potency. A meticulous examination of the structure-activity relationship indicated that halogen and methoxy substituents were the most efficacious. In silico investigations delved into induced fit docking, pharmacokinetics, and molecular dynamics simulations to elucidate the intricate interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, our pharmacokinetic assessments confirmed that the majority of the synthesized compounds possess attributes conducive to potential drug 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 B.V. All rights reserved.)

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC 50 value of 0.40 ± 0.02 μM, ~2183-fold higher than acarbose having an IC 50 of 873.34 ± 1.67 μM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides ( 1 and 2 ) and their new sulfonyl hydrazone derivatives ( 9 - 20 ), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds ( 9 - 20 ) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1 H-, and 13 C-NMR. The antiproliferative profiles of these compounds ( 1 , 2 , and 9 - 20 ) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2 , other compounds ( 9 - 20 ) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds ( 9 - 20 ) demonstrated antiproliferative activities at a micromolar level, with IC 50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC 50 = 29.59 μM against A549 cell line and IC 50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC 50 = 22.42 μM against A549 cell line and IC 50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski's rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

Volatile oils or essential oils (EOs) were extracted from three V. sebifera samples (labeled as A, B, and C) in September 2018 and February 2019; the extraction process involved hydrodistillation of the leaves. The chemical compositions of the EOs were analyzed using gas chromatography-mass spectrometry (GC/MS). The volatile components were identified by comparing their retention indices and mass spectra with standard substances documented in the literature (ADAMS). The antioxidant activity of the EOs was evaluated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), while their toxicity was assessed using Artemia salina Leach. Molecular docking was utilized to examine the interaction between the major constituents of V. sebifera EO and acetylcholinesterase (AChE), a molecular target linked to toxicity in A. salina models. The EO obtained from specimen A, collected in September 2018, was characterized by being primarily composed of (E,E)-α-farnesene (47.57%), (E)-caryophyllene (12.26%), and α-pinene (6.93%). Conversely, the EO from specimen A, collected in February 2019, was predominantly composed of (E,E)-α-farnesene (42.82%), (E)-caryophyllene (16.02%), and bicyclogermacrene (8.85%), the EO from specimen B, collected in September 2018, primarily contained (E,E)-α-farnesene (47.65%), (E)-caryophyllene (19.67%), and α-pinene (11.95%), and the EO from the leaves collected in February 2019 was characterized by (E,E)-α-farnesene (23.57%), (E)-caryophyllene (19.34%), and germacrene D (7.33%). The EO from the leaves collected in September 2018 contained (E,E)-α-farnesene (26.65%), (E)-caryophyllene (15.7%), and germacrene D (7.72%), while the EO from the leaves collected in February 2019 was primarily characterized by (E,E)-α-farnesene (37.43%), (E)-caryophyllene (21.4%), and α-pinene (16.91%). Among these EOs, sample B collected in February 2019 demonstrated the highest potential for inhibiting free radicals, with an inhibition rate of 34.74%. Conversely, the EOs from specimen A exhibited the highest toxic potentials, with an lethal concentration 50 (LC 50 ) value of 57.62 ± 1.53 µg/mL, while specimen B had an LC 50 value of 74.72 ± 2.86 µg/mL. Molecular docking results suggested that hydrophobic interactions significantly contributed to the binding of the major compounds in the EO from sample B to the binding pocket of AChE.

Lamiaceae (Labiatae) is a medicinally significant plant family featuring key species like Salvia aegyptiaca, S. cabulica, S. coccinea, S. glutinosa, S. officinalis, S. haematodes, S. hians, S. lanata, S. macrosiphon, S. moorcroftiana, S. spinosa, S. sclarea, and S. plebeia. These species exhibit diverse pharmacological activities attributed to essential oils and phytochemi-cals, including antioxidant, antiasthmatic, antitumor, anti-inflammatory, analgesic, etc. This re-view covers extensive phytomedicinal aspects of some important plants of the genus Salvia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Carbonic anhydrase CA-II enzyme is essential for maintaining homeostasis in several processes, including respiration, lipogenesis, gluconeogenesis, calcification, bone resorption, and electrolyte balance due to its vital function within cellular processes. Herein, we screened 25 newly synthesized thiazole derivatives and assessed their inhibitory potential against the zinc-containing carbonic anhydrase CA-II enzyme. Intriguingly, derivatives of thiazole exhibited varying degrees of inhibitory action against CA-II. The distinctive attribute of these compounds is that they can attach to the CA-II binding site and block its action. Morpholine based thiazoles can be strategically modified to improve bovine CA-II inhibitor binding affinity, selectivity, and pharmacokinetics. Thiazole and morpholine moieties can boost inhibitory efficacy and selectivity over other calcium-binding proteins by interacting with target bovine CA-II binding sites. The derivatives 23-26 exhibited greater affinity when compared to the standard acetazolamide. Furthermore, kinetic study of the most potent compound 24 was performed, which exhibited concentration dependent inhibition with a K i value of 9.64 ± 0.007 μM. Molecular docking, MD simulation and QSAR analysis was also carried out to elucidate the interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, pharmacokinetic assessments showed that most of the compounds possess attributes conducive to potential drug development., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

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.)

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate., (© 2024. The Author(s).)

In the past, efforts have been made to find a cure for diabetes, mainly evaluating new classes of compounds to explore their potency. In this study, we present the synthesis and evaluation of carbonylbis(hydrazine-1-carbothioamide) derivatives as potential α-glucosidase inhibitors, employing both in vivo and in silico investigations. The in vitro experiments revealed that all tested compounds were significantly potent for α-glucosidase inhibition, with the lead compound 3a displaying approximately 80 times higher activity than acarbose. To delve deeper, in silico induced fit docking, pharmacokinetics, and molecular dynamics studies were conducted. Significantly, compound 3a exhibited a docking score of -7.87 kcal/mol, surpassing acarbose, which had a docking score of -6.59 kcal/mol. The in silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development. Molecular dynamics analysis demonstrated that, when the ligand 3a was coupled with the target 3TOP, Cα-RMSD backbone RMSD values below 2.4 Å and "Lig_fit_Prot" values below 2.7 Å were observed. QSAR analysis demonstrates that the "fOC8A" descriptor positively correlates with α-glucosidase inhibition activity, while "lipoplus_AbSA" positively contributes and "notringC_notringO_8B" negatively contributes to this activity., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

The essential oils and aroma derived from the leaves (L), stems (St), and spikes (s) of Piper nigrum L. cv. Guajarina were extracted; the essential oils were extracted using hydrodistillation (HD), and steam distillation (SD), and the aroma was obtained by simultaneous distillation and extraction (SDE). Chemical constituents were identified and quantified using GC/MS and GC-FID. Preliminary biological activity was assessed by determining the toxicity against Artemia salina Leach larvae, calculating mortality rates, and determining lethal concentration values (LC 50 ). The predominant compounds in essential oil samples included α-pinene (0-5.6%), β-pinene (0-22.7%), limonene (0-19.3%), 35 linalool (0-5.3%), δ-elemene (0-10.1%), β-caryophyllene (0.5-21.9%), γ-elemene (7.5-33.9%), and curzerene (6.9-31.7%). Multivariate analysis, employing principal component analysis (PCA) and hierarchical cluster analysis (HCA), revealed three groups among the identified classes and two groups among individual compounds. The highest antioxidant activity was found for essential oils derived from the leaves (167.9 41 mg TE mL -1 ). Larvicidal potential against A. salina was observed in essential oils obtained from the leaves (LC50 6.40 μg mL -1 ) and spikes (LC 50 6.44 μg mL -1 ). The in silico studies demonstrated that the main compounds can interact with acetylcholinesterase, thus showing the potential molecular interaction responsible for the toxicity of the essential oil in A. salina .

Introduction: The aromatase enzyme plays an important role in the progress of hormone-dependent breast cancer, especially in estrogen receptor-positive (ER+) breast cancers. In case of postmenopausal women, the aromatization of androstenedione to estrone in adipose tissue is the most important source of estrogen. Generally 60%-75% of pre- and post-menopausal women suffer from estrogen-dependent breast cancer, and thus suppressing estrogen has been recognized to be a successful therapy. Hence, to limit the stimulation of estrogen, aromatase inhibitors (AIs) are used in the second-line treatment of breast cancer., Methods: The present computational study employed an in silico approach in the identification of natural actives targeting the aromatase enzyme from a structurally diverse set of natural products. Molecular docking, QSAR studies and pharmacophore modeling were carried out using the VLife Molecular Design Suite (version 4.6). The stability of the compounds was confirmed by molecular dynamics., Results: From molecular docking and analysis of interactions with the amino acid residues of the binding cavity, it was found that the amino acid residues interacting with the non-steroidal inhibitors exhibited π-stacking interactions with PHE134, PHE 221, and TRP 224, while the steroidal drug exemestane lacked π-stacking interactions. QSAR studies were performed using the flavonoid compounds, in order to identify the structural functionalities needed to improve the anti-breast cancer activity. Molecular dynamics of the screened hits confirmed the stability of compounds with the target in the binding cavity. Moreover, pharmacophore modelling presented the pharmacophoric features of the selected scaffolds for aromatase inhibitory activity., Conclusion: The results presented 23 hit compounds that can be developed as anti-breast cancer modulating agents in the near future. Additionally, anthraquinone compounds with minor structural modification can also serve to be potential aromatase inhibitors. The in silico protocol utilised can be useful in the drug discovery process for development of new leads from structurally diverse set of natural products that are comparable to the drugs used clinically in breast cancer therapy., Competing Interests: There are no competing interests to declare., (© 2024 The Author(s).)

Cancer is a disease that affects people of all ages, socioeconomic backgrounds, genders, and demographics. It places a significant burden not just on those who are diagnosed but also on their families and communities. Targeted therapeutic medications have surpassed more conventional forms of chemotherapy in terms of both their effectiveness and safety, which leads to their rapid ascent to the forefront of cancer treatment. A growing number of small molecules have been created for the treatment of cancer, and several of these drugs have been approved to be sold in the market by the Food and Drug Administration of the United States. Small molecule targeted anticancer therapies have made significant progress in recent years, yet they continue to struggle with a number of obstacles, including a low response rate and drug resistance. We have carried out an exhaustive study on approved small-molecule targeted anticancer medications, as well as important drug candidates. This review describes the significance of approved anticancer drugs from 2021 to 2024, clinically active anticancer drugs, and the methods used for their synthesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neglected tropical diseases (NTDs) are prevalent in tropical and subtropical countries, and schistosomiasis is among the most relevant diseases worldwide. In addition, one of the two biggest problems in developing drugs against this disease is related to drug resistance, which promotes the demand to develop new drug candidates for this purpose. Thus, one of the drug targets most explored, Schistosoma mansoni Cathepsin B1 (SmCB1 or Sm31), provides new opportunities in drug development due to its essential functions for the parasite's survival. In this way, here, the latest developments in drug design studies targeting SmCB1 were approached, focusing on the most promising analogs of nitrile, vinyl sulphones, and peptidomimetics. Thus, it was shown that despite being a disease known since ancient times, it remains prevalent throughout the world, with high mortality rates. The therapeutic arsenal of antischistosomal drugs (ASD) consists only of praziquantel, which is widely used for this purpose and has several advantages, such as efficacy and safety. However, it has limitations, such as the impossibility of acting on the immature worm and exploring new targets to overcome these limitations. SmCB1 shows its potential as a cysteine protease with a catalytic triad consisting of Cys 100 , His 270 , and Asn 290 . Thus, design studies of new inhibitors focus on their catalytic mechanism for designing new analogs. In fact, nitrile and sulfonamide analogs show the most significant potential in drug development, showing that these chemical groups can be better exploited in drug discovery against schistosomiasis. We hope this manuscript guides the authors in searching for promising new antischistosomal drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. Results: The synthesized compounds, particularly compound 5 , exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound 5 altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.7-fold) and late stages (33-fold), while moderately affecting necrotic signaling. The antitumor activity was linked to a notable reduction (4.78-fold) in topoisomerase IIβ expression. Molecular modeling indicated compound 5 's strong affinity for EGFR, human EGF2 and topoisomerase II proteins. Conclusion: These findings highlight compound 5 as a multifaceted antitumor agent for breast cancer.

Despite extensive genetic and biochemical characterization, the molecular genetic basis underlying the biosynthesis of β-diketones remains largely unexplored. β-Diketones and their complexes find broad applications as biologically active compounds. In this study, in silico molecular docking results revealed that two β-diketone derivatives, namely 2-(2-(4-fluorophenyl)hydrazono)-5,5-dimethylcyclohexane-1,3-dione and 5,5-dimethyl-2-(2-(2-(trifluoromethyl)phenyl)hydrazono)cyclohexane-1,3-dione, exhibit anti-COX-2 activities. However, recent docking results indicated that the relative anti-COX-2 activity of these two studied β-diketones was influenced by the employed docking programs. For improved design of COX-2 inhibitors from β-diketones, we conducted molecular dynamics simulations, density functional theory (DFT) calculations, Hirshfeld surface analysis, energy framework, and ADMET studies. The goal was to understand the interaction mechanisms and evaluate the inhibitory characteristics. The results indicate that 5,5-dimethyl-2-(2-(2-(trifluoromethyl)phenyl)hydrazono)cyclohexane-1,3-dione shows greater anti-COX-2 activity compared to 2-(2-(4-fluorophenyl)hydrazono)-5,5-dimethylcyclohexane-1,3-dione.

Breast cancer is a global health concern, with increasing disease burden and disparities in access to healthcare. Late diagnosis and limited treatment options in underserved areas contribute to poor outcomes. In response to this challenge, we developed a novel family of 2-substituted-quinoxaline analogues, combining coumarin and quinoxaline scaffolds known for their anticancer properties. Through a versatile synthetic approach, we designed, synthesized, and characterized a set of 2-substituted quinoxaline derivatives. The antiproliferative activity of the synthesized compounds was assessed toward the MCF-7 breast cancer cells. Our investigations showed that the synthesized compounds exhibit considerable antiproliferative activity toward MCF-7 cells. Notably, compound 3b, among examined compounds, displayed a superior inhibitory effect (IC 50 = 1.85 ± 0.11 μM) toward the growth of MCF-7 cells compared to the conventional anticancer drug staurosporine (IC 50 = 6.77 ± 0.41 μM) and showed minimal impact on normal cells (MCF-10A cell lines, IC 50 = 33.7 ± 2.04 μM). Mechanistic studies revealed that compound 3b induced cell cycle arrest at the G1 transition and triggered apoptosis in MCF-7 cells, as evidenced by increasing the percentage of cells arrested in the G2/M and pre-G1 phases utilizing flow cytometric analysis and Annexin V-FITC/PI analysis. Moreover, compound 3b was found to substantially suppress topoisomerase enzyme activity in MCF-7 cells. Molecular modeling studies further supported the potential of compound 3b as a therapeutic candidate by demonstrating significant binding affinity to the active sites of both topoisomerase II and EGFR proteins. Taken together, the presented 2-substituted-quinoxaline analogues, especially compound 3b, show promise as potential candidates for the development of effective anti-breast cancer drugs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Type-2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders in the world and over the past three decades its incidence has increased drastically. α-Glucosidase inhibitors are used to control the hyperglycemic affect of T2DM. Herein, we report the synthesis, α-glucosidase inhibition, structure activity relationship, pharmacokinetics and docking analysis of various novel chromone based thiosemicarbazones 3(a-r). The derivatives displayed potent activity against α-glucosidase with IC 50 in range of 0.11 ± 0.01-79.37 ± 0.71 µM. Among all the synthesized compounds, 3a (IC 50  = 0.17 ± 0.026 µM), 3 g (IC 50  = 0.11 ± 0.01 µM), 3n (IC 50  = 0.55 ± 0.02 µM), and 3p (IC 50  = 0.43 ± 0.025 µM) displayed higher inhibitory activity as compared to the standard, acarbose. Moreover, we have developed a statistically significant 2D-QSAR model (R 2 tr :0.9693; F: 50.4647 and Q 2 LOO :0.9190), which can be used in future to further design potent thiosemicarbazones as inhibitors of α-glucosidase., 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 © 2023 Elsevier Inc. All rights reserved.)

Originating in Wuhan, the COVID-19 pandemic wave has had a profound impact on the global healthcare system. In this study, we used a 2D QSAR technique, ADMET analysis, molecular docking, and dynamic simulations to sort and evaluate the performance of thirty-nine bioactive analogues of 9,10-dihydrophenanthrene. The primary goal of the study is to use computational approaches to create a greater variety of structural references for the creation of more potent SARS-CoV-2 3Clpro inhibitors. This strategy is to speed up the process of finding active chemicals. Molecular descriptors were calculated using 'PaDEL' and 'ChemDes' software, and then redundant and non-significant descriptors were eliminated by a module in 'QSARINS ver. 2.2.2'. Subsequently, two statistically robust QSAR models were developed by applying multiple linear regression (MLR) methods. The correlation coefficients obtained by the two models are 0.89 and 0.82, respectively. These models were then subjected to internal and external validation tests, Y-randomization, and applicability domain analysis. The best model developed is applied to designate new molecules with good inhibitory activity values against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). We also examined various pharmacokinetic properties using ADMET analysis. Then, through molecular docking simulations, we used the crystal structure of the main protease of SARS-CoV-2 (3CLpro/Mpro) in a complex with the covalent inhibitor "Narlaprevir" (PDB ID: 7JYC). We also supported our molecular docking predictions with an extended molecular dynamics simulation of a docked ligand-protein complex. We hope that the results obtained in this study can be used as good anti-SARS-CoV-2 inhibitors., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier B.V.)

The essential oils (OEs) of the leaves, stems, and spikes of P. marginatum were obtained by hydrodistillation, steam distillation, and simultaneous extraction. The chemical constituents were identified and quantified by GC/MS and GC-FID. The preliminary biological activity was determined by assessing the toxicity of the samples to Artemia salina Leach larvae and calculating the mortality rate and lethal concentration (LC 50 ). The antioxidant activity of the EOs was determined by the DPPH radical scavenging method. Molecular modeling was performed using molecular docking and molecular dynamics, with acetylcholinesterase being the molecular target. The OES yields ranged from 1.49% to 1.83%. The EOs and aromatic constituents of P. marginatum are characterized by the high contents of ( E )-isoosmorhizole (19.4-32.9%), 2-methoxy-4,5-methylenedioxypropiophenone (9.0-19.9%), isoosmorhizole (1.6-24.5%), and 2-methoxy-4,5-methylenedioxypropiophenone isomer (1.6-14.3%). The antioxidant potential was significant in the OE of the leaves and stems of P. marginatum extracted by SD in November (84.9 ± 4.0 mg TE·mL -1 ) and the OEs of the leaves extracted by HD in March (126.8 ± 12.3 mg TE·mL -1 ). Regarding the preliminary toxicity, the OEs of Pm-SD-L-St-Nov and Pm-HD-L-St-Nov had mortality higher than 80% in concentrations of 25 µg·mL -1 . This in silico study on essential oils elucidated the potential mechanism of interaction of the main compounds, which may serve as a basis for advances in this line of research.

Four species of the genus Hedychium can be found in Brazil. Hedychium coronarium is a species endemic to India and Brazil. In this paper, we collected six specimens of H. coronarium for evaluation of their volatile chemical profiles. For this, the essential oils of these specimens were extracted using hydrodistillation from plant samples collected in the state of Pará, Brazil, belonging to the Amazon region in the north of the country. Substance compounds were identified with GC/MS. The most abundant constituent identified in the rhizome and root oils was 1,8-cineole (rhizome: 35.0-66.1%; root: 19.6-20.8%). Leaf blade oil was rich in β-pinene (31.6%) and (E)-caryophyllene (31.6%). The results from this paper allow for greater knowledge about the volatile chemical profile of H. coronarium specimens, in addition to disseminating knowledge about the volatile compounds present in plant species in the Amazon region.

This study examines the potential of Cannabis sativa L. plants to be repurposed as therapeutic agents for cancer treatment through designing of hybrid Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). A set of 50 phytochemicals was taken from Cannabinoids and Terpenes and subjected for screening using Semi-flexible and Flexible Molecular Docking methods, MM-GBSA free binding energy computations, and pharmacokinetic/pharmacodynamic (ADME-Tox) predictions. Nine promising phytochemicals, Cannabidiolic acid (CBDA), Cannabidiol (CBD), Tetrahydrocannabivarin (THCV), Dronabinol (Δ-9-THC), Delta-8-Tetrahydrocannabinol (Δ-8-THC), Cannabicyclol (CBL), Delta9-tetrahydrocannabinolic acid (THCA), Beta-Caryophyllene (BCP), and Gamma-Elemene (γ-Ele) were identified as potential EGFR-TKIs natural product candidates for cancer therapy. To further validate these findings, a set of Molecular Dynamics simulations were conducted over a 200 ns trajectory. This hybrid early drug discovery screening strategy has the potential to yield a new generation of EGFR-TKIs based on natural cannabis products, suitable for cancer therapy. In addition, the application of this computational strategy in the virtual screening of both natural and synthetic chemical libraries could support the discovery of a wide range of lead drug agents to address numerous diseases., Competing Interests: The authors reported in the manuscript has no any conflict of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

Surfactants are a group of amphiphilic molecules (i.e., having both hydrophobic and hydrophilic domains) that are a vital part of nearly every contemporary industrial process such as in agriculture, medicine, personal care, food, and petroleum. In general surfactants can be derived from (i) petroleum-based sources or (ii) microbial/plant origins. Petroleum-based surfactants are obvious results from petroleum products, which lead to petroleum pollution and thus pose severe problems to the environment leading to various ecological damages. Thus, newer techniques have been suggested for deriving surfactant molecules and maintaining environmental sustainability. Biosurfactants are surfactants of microbial or plant origins and offer much added advantages such as high biodegradability, lesser toxicity, ease of raw material availability, and easy applicability. Thus, they are also termed "green surfactants". In this regard, this review focused on the advantages of biosurfactants over the synthetic surfactants produced from petroleum-based products along with their potential applications in different industries. We also provided their market aspects and future directions that can be considered with selections of biosurfactants. This would open up new avenues for surfactant research by overcoming the existing bottlenecks in this field., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as 1 H-NMR, 13 C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 suggested that all compounds essentially exhibited activity against selected strains of bacteria. Our DFT analyses suggested that the compounds of the SM-IMP-01-SM-IMP-13 series have HOMO/LUMO gaps within 4.43-4.69 eV, whereas the compounds of the DA-01-DA-05 series have smaller values of the HOMO/LUMO gaps, 3.24-4.17 eV. The lowest value of the global hardness and the highest value of the global softness, 2.215 and 0.226 eV, respectively, characterize the compound SM-IMP-02; thus, it is the most reactive compound in the imidazopyridine carboxamide series (except hydrazide series). This compound also depicted lesser MIC values against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 as 4.8 µg/mL, each. In terms of another series, hydrazide DA-05 depicted strong antimicrobial actions (MIC: 4.8 µg/mL against both bacterial strains) and also had the lowest energy gap (3.24 eV), higher softness (0.309 eV), and lesser hardness (1.62 eV). Overall, when we compare qualitative and quantitative antimicrobial results, it is been very clear that compounds with dibromo substitutions on imidazopyridine (IMP) rings would act as better antimicrobial agents than those with -H at the eighth position on the IMP ring. Furthermore, substituents of higher electronegativities would tend to enhance the biological activities of dibromo-IMP compounds. DFT properties were also well comparable to this trend and overall, we can say that the electronic behavior of compounds under investigation has key roles in their bioactivities., Competing Interests: The authors declare no conflicts of interest.

The abnormal expression of the c-Met tyrosine kinase has been linked to the proliferation of several human cancer cell lines, including non-small-cell lung cancer (NSCLC). In this context, the identification of new c-Met inhibitors based on heterocyclic small molecules could pave the way for the development of a new cancer therapeutic pathway. Using multiple linear regression (MLR)-quantitative structure-activity relationship (QSAR) and artificial neural network (ANN)-QSAR modeling techniques, we look at the quantitative relationship between the biological inhibitory activity of 40 small molecules derived from cyclohexane-1,3-dione and their topological, physicochemical, and electronic properties against NSCLC cells. In this regard, screening methods based on QSAR modeling with density-functional theory (DFT) computations, in silico pharmacokinetic/pharmacodynamic (ADME-Tox) modeling, and molecular docking with molecular electrostatic potential (MEP) and molecular mechanics-generalized Born surface area (MM-GBSA) computations were used. Using physicochemical (stretch-bend, hydrogen bond acceptor, Connolly molecular area, polar surface area, total connectivity) and electronic (total energy, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels) molecular descriptors, compound 6d is identified as the optimal scaffold for drug design based on in silico screening tests. The computer-aided modeling developed in this study allowed us to design, optimize, and screen a new class of 36 small molecules based on cyclohexane-1,3-dione as potential c-Met inhibitors against NSCLC cell growth. The in silico rational drug design approach used in this study led to the identification of nine lead compounds for NSCLC therapy via c-Met protein targeting. Finally, the findings are validated using a 100 ns series of molecular dynamics simulations in an aqueous environment on c-Met free and complexed with samples of the proposed lead compounds and Foretinib drug., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In search of new anti-breast cancer agents, the present study envisaged the design and synthesis of a series of benzopyran-chalcones. All the synthesized compounds were assayed for their in-vitro anticancer activity against ER + MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines using SRB assay. The synthesized compounds were found active against ER + MCF-7 cell lines. Based on the in-vitro data, in-silico analysis was performed using hormone-dependent breast cancer targets such as hER-α and aromatase because the compounds showed activity against MCF-7 cells and none was active against MDA-MB-231. The in-silico results supported the in-vitro anticancer activity suggesting the affinity of compounds toward hormone-dependant breast cancer. Compounds 4A1 to 4A3 were found to be most cytotoxic to MCF-7 cells with IC 50 values of 31.87, 22.95, and 20.34 μg/ml, respectively (Doxorubicin IC 50 : <10 μg/ml). In addition, they showed the interactions with the amino acid residues of a binding cavity of an hER-α. Furthermore, quantitative structure-activity relationship (QSAR) studies were performed to reveal the vital structural features required for anticancer activity against breast cancer. Molecular dynamic simulation studies of hER-α and 4A3 in comparison with the raloxifene complex ensure the appropriate refinement of compounds in the dynamic system. Additionally, a generated pharmacophore model explored the essential pharmacophoric features of the synthesized scaffolds with respect to clinically used drug molecules for optimal hormone-dependant anti-breast cancer activity.Communicated by Ramaswamy H. Sarma.

Background: Hydrazide-hydrazone derivatives have shown diverse biological activities, such as antitubercular (anti-TB), antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal actions., Objectives: Hydrazide-hydrazones contain azomethine (-NH-N=CH-) group connected with carbonyl group and are believed to be responsible for various pharmaceutical applications. They aid in the synthesis of different five-membered heterocyclic systems, such as oxadiazole, triazoles, etc. Methods: In the present study, various hydrazines/hydrazones were synthesized starting from 4- amino benzoic acid derivatives. Structures of all 9 newly synthesized compounds (6a-6d and 8a- 8e) were further characterized by using various spectroscopic methods, such as 1 H-NMR (Nuclear Magnetic Resonance), FT-IR (Fourier-transform infrared spectroscopy), Gas chromatographymass spectrometry (GC-MS), etc. Furthermore, molecular docking analysis against the acyl-CoA carboxylase, AccD5 (PDB ID: 2A7S), was also carried out using the Glide module, which depicted good binding scores than standard drugs. The anti-tuberculosis activity of all the hydrazides and hydrazones (6a-6d and 8a-8e) were evaluated against the Mycobacterium tuberculosis H37 RV strain using the Alamar-Blue susceptibility (MABA) test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL values. The antioxidant activity was also carried out using a DPPH assay., Results: Our findings demonstrated highly encouraging in-vitro results (MABA assay, MIC: 1.2 μg/mL) of hydrazones as depicted by good antimycobacterial activity. The antioxidant results showed a moderate to a good percentage of DPPH inhibition. Our in-silico ADMET analysis further suggested good pharmacokinetic and toxicity-free profiles of synthesized analogues ( 6a-6d and 8a-8e )., Conclusion: Our results signify hydrazones/hydrazines as potential hit candidates against the future developments of potent and safer anti-TB agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The human respiratory syncytial virus (RSV) is responsible for causing upper and lower respiratory tract infections in young children. RSV Fusion (F) protein is a surface glycoprotein that facilitates virus entry into host cells. Thus, newer designing of RSV Fusion (F) protein inhibitors is required on an urgent basis., Methods: In the present study, we have developed statistically robust. Quantitative structure-activity relationship (QSAR) models for the effective designing of newer analogues of piperazinylquinoline derivatives (H1-H12)., Results: Our developed models were retained with high statistical parameters (R 2 > 0.6 and Q 2 > 0.5). Our developed pharmacophore, model (AADHRR&#95;2) (indicating that two hydrogen bond acceptors, one hydrogen bond donor, one hydrophobic group, and two aromatic rings) is crucial for retaining the activities of piperazinylquinoline derivatives against RSV. Moreover, docking analysis of 12 new analogues on RSV pre-F in complex with 5C4 Fab (PDB ID: 5W23) and post-F trimeric protein (PDB ID: 3RRR) suggested higher affinities of these molecules against studied targets with good docking scores., Conclusion: Thus, one can implement developed QSAR models, docking analogy and Pharmacophore models for identifications of potent leads for designed molecules as RSV Fusion (F) protein inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hydrazone and its azomethine (-NHN=CH-) derivatives are widely reported for their immense pharmacological potential. They have also been reported to possess potent anti-tuberculosis, anti-malarial, anti-inflammatory, and anti-oxidant activities. Considering their pharmacological significance, we herein synthesized a set of 10 hydrazones (1S-10S) using green, biodegradable chitosan and HCl as catalyst., Methods: All synthesized compounds were characterized using modern spectroscopic techniques, including Nuclear magnetic resonance, 1H-/13C-NMR; Fourier transform infrared spectroscopy (FT-IR); Ultraviolet-visible spectroscopy; Mass spectrometry (m/z), etc. Synthesized compounds were in silico screened using molecular docking, dynamics, pharmacokinetics, theoretical properties, and common pharmacophore analysis. Moreover, we also subjected all compounds to DPPH radical scavenging assay, protein denaturation assay, Trypan Blue assay for cell viability assessments, β-hematin assay for hemozoin inhibition analysis and standard antimicrobial analysis., Results: Our results suggested that the synthesized compound 2S had high potency against studied microbial strains (minimum MIC = 3.12 μg/mL). Our antioxidant analysis for 1S-10S revealed that our compounds had radical scavenging effects ranging from 25.1-80.3 %. Compounds 2S exhibited % cell viability of 68.92% (at 100 μg concentration of sample), while the same compound retained anti-inflammatory % inhibition at 62.16 %. Compound 2S was obtained as the best docked molecule, with a docking score of -5.32 Kcal/mol with target pdb id: 1d7u protein. Molecular dynamics simulation and normal mode analysis for 100 ns for 1d7u:2S retained good stability. Finally, in silico pharmacokinetics, theoretical properties and pharmacophoric features were assessed., Conclusion: In summary, synthesized hydrazone exhibited a good biological profile according to in silico and in vitro studies. However, further in vivo studies are required that may shed more insights on its potencies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: L-proline is a natural amino acid having secondary amine functionality and acts as a bifunctional catalyst (organo-catalyst). The amino-functional group acts as Lewis base type while carboxylic acids act as Brønsted acid type catalysts. It catalyzed different asymmetric syntheses, including known reactions such as Aldol condensation, Mannich reaction, Michael Addition, Knoevenagel condensation, Hantzsch synthesis, OXA-Michael Henry tandem, Ullmann reactions, Wieland-Miescher ketone synthesis, Robinson annulation, Biginelli reaction, α- amination. It is also an essential catalyst for synthesizing heterocyclic skeletons such as coumarin, spiro-oxindoles, imidazoles, benzimidazoles, quinoxalines, podophyllotoxin, benzothiazoles, isoxazolidines, phenothiazines, aziridine, indole, 1,5-benzodiazepines, pyridine, and quinazolines., Objective: In this review, we had the objective to critically summarize the use of proline and proline derivatives as catalysts of multicomponent reactions performed in various media and leading to synthetically and biologically relevant heterocycles, a very important class of compounds that constitutes over 60% of drugs and agrochemicals., Methods: All scholarly articles for L-Proline catalyzed reactions were retrieved from ScienceDirect, Google Scholar , PubMed, etc. Results and Conclusion: Given the importance of L-Proline based reactions, it has been observed to have tremendous applications in organic chemistry. It can also act as a 'Green catalyst'., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Croton campinarensis Secco, A. Rosário & PE Berry is an aromatic species recently discovered in the Amazon region. This study first reports the chemical profile, antioxidant capacity, and preliminary toxicity to A. salina Leach of the essential oil (EO) of this species. The phytochemical profile of the essential oil was analyzed by gas chromatography (GC/MS) and (GC-FID). The antioxidant capacity of the EO was measured by its inhibition of ABTS •+ and DPPH • radicals. Molecular modeling was used to evaluate the mode of interaction of the major compounds with acetylcholinesterase (AChE). The results indicate that the EO yield was 0.24%, and germacrene D (26.95%), bicyclogermacrene (17.08%), ( E )-caryophyllene (17.06%), and δ-elemene (7.59%) were the major compounds of the EO sample. The EO showed a TEAC of 0.55 ± 0.04 mM·L -1 for the reduction of the ABTS •+ radical and 1.88 ± 0.08 mM·L -1 for the reduction of the DPPH • radical. Regarding preliminary toxicity, the EO was classified as toxic in the bioassay with A. salina (LC 50 = 20.84 ± 4.84 µg·mL -1 ). Through molecular docking, it was found that the majority of the EO components were able to interact with the binding pocket of AChE, a molecular target related to toxicity evaluated in A. salina models; the main interactions were van der Waals and π-alkyl interactions.

Tuberculosis (TB) is one of the emerging infectious diseases in the world. DprE1 (Decaprenylphosphoryl-β-D-ribose 2'-epimerase), an enzyme accountable for mycobacterial cell wall synthesis was the first drug gable target based on discoveries of inhibitors via HTS (high throughput screening). Since then, many literature reports have been published so far enlightening varieties of chemical scaffolds acting as inhibitors of DprE1. Herein, in our present study, we have developed statistically robust GA-MLR (genetic algorithm multiple linear regression), atom-based as well as field based-3D-QSAR models. Both atom-based as well as field based-3D-QSAR models (internally as well as externally validated) were obtained with robust Training set, R 2  > 0.69 and Test set, Q 2  > 0.50. We have also developed top ranked 5 point hypothesis AAAHR&#95;1 among 14 CPHs (common pharmacophore hypotheses). We found that our dataset molecule had more docking score (XP mode = - 9.068 kcal/mol) than the standards isoniazid and ethambutol; when docked into binding pockets of enzyme 4P8C with Glide module. We further queried our best docked dataset molecule 151 for ligand based virtual screening using "SwissSimilarity" platform. Among 9 identified hits, we found ZINC12196803 had best binding energies and docking score (docking score = - 9.437 kcal/mol, MMGBSA dgBind = - 70.508 kcal/mol). Finally, our molecular dynamics studies for 1.2-100 ns depicts that these complexes are stable. We have also carried out in-silico ADMET predictions, Cardiac toxicity, 'SwissTargetPredictions' and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding energy calculations for further explorations of dataset as well as hit molecules. Our current studies showed that the hit molecule ZINC12196803 may enlighten the path for future developments of DprE1 inhibitors., (© 2022. The Author(s).)

The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund's adjuvant (CFA) induced pain model. The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 & 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours. Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity. This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Thiadiazoles can be considered as the privileged scaffold having diverse pharmacological potentials such as antihypertensive, anti-HIV, antimicrobials, antileishmanial agents, etc. In particular, 1,2,5-thiadiazoles and their fused analogues are subjects of fast-growing interest due to their higher significance in the fields of biomedicine and material sciences., Objective: This study aims to collect detailed medicinal information about aspects of 1,2,5- thiadiazole., Methods: A systemic search has been carried out using PubMed, Google Scholar, CNKI, etc., for relevant studies having the keyword, '1,2,5-thiadiazole'., Results and Conclusion: In this mini-review, we have covered known procedures of the synthesis and explored in details all known advancements of this scaffold concerning to its biological activities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Mycobacterium tuberculosis (Mtb) is an organism that causes tuberculosis (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones- hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication., Objectives: We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature., Materials and Methods: All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial activity against H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors., Results: Among all tested molecules, 3i (MIC: 50 μg/mL) and 3b (MIC: 50 μg/mL) were found to be the best ligands for further development of new anti-TB drug. We found that our proposed molecules have higher docking scores, corresponding standard anti-TB agents, such as ciprofloxacin and isoniazid. Synthesized compounds were found to have druglikeness properties when tested with Lipinski's filter for drug-likeness., Conclusion: Our current study proposes N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for development into active lead molecules., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Malaria is responsible for social and economic burden in most lowincome malaria-affected countries. Thus, newer antimalarials are needed to tackle morbidities and mortalities associated with the drug-resistant malarial strains. Haemoglobin digestion inside the food vacuole of malarial parasite would lead to producing redox-active and toxic-free heme. The detoxification process adopted by Plasmodium sp. would give rise to hemozoin (Hz) (betahematin) formation. Targeting the pathway of hemozoin formation is considered a validated target for the discovery of newer antimalarials., Objective: This study aims to collect detailed information about aspects of hemozoin (Hz) (betahematin) inhibitors., Methods: A systemic search has been carried out using PubMed, Google Scholar, CNKI, etc., for relevant studies having the keyword, 'hemozoin or beta-hematin' for almost the last 2 decades (2000-2021)., Results: This review tries to summarize all the recent advancements made for the developments of synthetic, natural isolated phytoconstituents and plant extracts inhibiting the hemozoin (betahematin) formation., Conclusion: Thus they would act as promising antimalarial candidates in the near future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A green protocol for the synthesis of unsubstituted imidazoles has been demonstrated herein. The reaction is realized using commercially available lipase enzyme, porcine pancreas lipase (PPL) in water. The reaction conditions are selective and mild which helped to tolerate a wide variety of functional groups to give the desired products in good chemical yields.[Formula: see text].

Anxiety is an unpleasant state, which can critically decrease the quality of life is often accompanied by nervous behaviour and rumination. Niranthin is a lignan isolated from various Phyllanthus sources. The literature survey on niranthin highlights wide ranges of the therapeutic potentials. In a present study, based on our previous investigations, we evaluated pure, isolated and characterized niranthin as an anxiolytic agent. The niranthin [6-[(2R,3R)-3-[(3,4-dimethoxyphenyl)methyl]-4-methoxy-2-(methoxymethyl)butyl]-4-methoxy-1,3-benzodioxole] was purchased from commercial source and further subjected for assessment of its anxiolytic potentials using popular animal models including Elevated plus-maze model/test (EPM) and Light & Dark Exploration test (L&D). GABA-A receptor mediation was evaluated by pretreating the mice with the GABA-A receptor antagonist Flumazenil before the EPM task. Molecular docking simulation studies (pdb id: 4COF) carried out by Vlife QSAR software showed that niranthin (docking score: - 62.1714 kcal/mol) have shown comparatively best docking score compared to the standard drug Diazepam (docking score: - 63.1568 kcal/mol). To conclude, Niranthin has probable potential in the management of anxiety disorder. Our in-silico and in-vivo analysis (indirectly) indicated the plausible role of GABA mediation for anxiolytic activity. Although, these studies are preliminary, future in depth experimental explorations will be required to use Niranthin as anti-anxiety drug in near future.

The extracts and the compounds isolated from Phyllanthus amarus Schumm and Thonn (Family: Euphorbiaceae) have shown a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective, nephroprotective and diurectic properties., Background: This investigation was aimed at exploring the anxiolytic potential of Phyllanthus amarus standardized extracts and predict probable role of marker phyto constitutents., Objective and Methods: Three standardized extracts of Phyllanthus amarus plant viz. standardized aqueous extract of Phyllanthus amarus whole plant (PAAE), standardized methanolic extract of P. amarus leaf (PAME) and the standardized hydro-methanolic extract of P. amarus leaf (PAHME) were tested in the classical animal models of anxiety: Elevated plus-maze model and Light & Dark Exploration test., Results: The lower doses of the tannin rich extract (PAHME) of the P. amarus possess significant anxiolytic activity compared to lignin rich (PAME) and aqueous extracts (PAAE), while at a higher dose (400mg/kg) the results of all three extracts appears to be potentially sedative. While the molecular docking studies support these probable anxiolytic, the sedative effects of the Phyllanthus amarus extracts could be due to the interaction of tannins and lignans with the GABAbenzodiazepine receptor complex., Conclusion: The results of the present study indicate that the tannin-rich extract of the P. amarus may have potential clinical applications in the management of anxiety. It can be further studied for optimum dosage to be used as a future of anti-anxiety drug development or as a standardized Phytomedicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tuberculosis (TB) is a major cause of mortality and illness as reported by the W.H.O in 2019. The WHO report also mentioned the fact that about 10.0 million people fell ill with tuberculosis in the year 2018. Hydrazide-hydrazones having azomethine group (-NH-N=CH-) connected with carbonyl group is reported for the number of bioactivities like anti-inflammatory, anticonvulsant, anticancer, antiviral and antiprotozoal., Objective: The objective of our current study is to design and synthesise more potent hydrazide- hydrazones, containing anti-tubercular agents., Methods: In the current study, we synthesized 10 hydrazones (3a-3j) by stirring corresponding benzohydrazides (2) with substituted aldehydes (1a-j) in ethanol as a solvent and acetic acid as a catalyst at room temperature. All synthesized compounds were characterized by various spectroscopic techniques including elemental analysis, ultraviolet-visible spectroscopy, fluorescence, fourier- transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Compounds (3a-3j) were tested for in vitro anti-TB activity using Microplate Alamar Blue Assay (MABA)., Results: All our synthesized compounds (3a-3j) were found to be potent against Mycobacteria tuberculosis (H37RV strain) with MIC (minimum inhibitory concentrations) values of 3.125-50 μg/mL. The hydrazide CO-NH protons in (3a-j) compounds are highly deshielded and showed broad singlet at 9.520-9.168 ppm. All the compounds were found to have more intense emission in the 416 - 429 nm regions and strong absorption in the regions of 316 - 327 nm. Synthesized compounds were also tested for in silico analysis using different software for their Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis. All the compounds were found to be in silico non-carcinogenic., Conclusion: It will be worth saying that our in silico and in vitro approaches used in the current study will become a guide for medicinal chemists to make structural modifications and synthesize more effective and potent hydrazone containing anti-tubercular agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: 1,8-diaminonaphthalen (1,8-DAN) with special organic structure was applied in organic synthesis to provide efficient complex scaffolds, through the two or fourcomponent fashion. This review highlights its recent application in organic reactions under different conditions and heterogynous catalysts to produce various molecules, which were used as medicines, sensors, and dyes., Objective: 1,8-diaminonaphthalene (1,8-DAN) is a bicyclic compound with two amino groups which has received much attention in organic chemistry due to their medicinal activities such as antifungal, antimicrobial, antiulcer, antitumor, oxidation dyestuff, hair color, fluorescent, and chemo-sensors. In continuation of our studies, herin, recent application of 1,8-DAN in organic synthesis was reviewed., Conclusion: In conclusion, the application of 1,8-DAN 1 in different reactions was reviewd through the various conditions to yield the target compounds with high medicinal activities, and potential for sensitive detection of different ions. The target compounds including 1,8-DAN 1 with various structures were provided such as perimidines, perimidinones, aminonaphthalenes which were produced through different methods as brought for further study in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: For the past several decades, the presence of tuberculosis (TB) is being remarked as the most common infectious disease leading to mortality., Objective: Hydrazone containing azometine group (-NHN=CH-) compounds have been reported for a broad range of bioactivities such as antiplatelet, analgesic, anti-inflammatory, anticonvulsant, antidepressant, antimalarial, vasodilator, antiviral, and antimicrobial, etc. Methods: For the synthesis of compounds (4a-4d) and (6a-6e), aromatic amines were treated with methyl terephthalaldehydate in methanol, giving Schiff's bases, followed by reductive amination and further treatment with hydrazine hydrate gave acid hydrazides (4a-4d). These acid hydrazides were then treated with different aromatic aldehydes to yield hydrazones (6a-6d). All the synthesized compounds were subjected to FT-IR, NMR, and UV spectroscopic characterization., Results: Compounds (4a-4d) and (6a-6e) were found to have highly potent activity against Mycobacteria tuberculosis (Vaccine strain, H37 RV strains): ATCC No- 27294 (MIC:1.6-6.25 μg/mL) than standard anti-TB drugs. The compounds exhibited good radical scavenging potentials(0- 69.2%), as checked from DPPH protocol. All compounds also demonstrated good in-silico ADMET results., Conclusion: The current study revealed promising in vitro anti-tuberculosis and anti-oxidant profiles of hydrazide-hydrazone analogues., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)