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In the search for new anticancer agents, we synthesized a new series of thiazole derivatives carried on thiadiazole-oxadiazole hybrid. Final compounds ( 5a-5i ) were analyzed via 1 H NMR, 13 C NMR, and HRMS. The pharmacokinetic profile of the targeted compounds was predicted via in silico calculations. Their anticancer properties were determined using MTT method against MCF7 and A549 cell lines. Compounds 5a , 5b and 5c were found more active against MCF7 cells than A549 cells while they were not cytotoxic on L929 healthy cells. Generally, it can be summarized that acetamide moiety has a pivotal role in anticancer activity. For further studies, their aromatase inhibitory activity was evaluated. After determination all these features, the binding modes of the active compounds and the stability and relation of the ligand-enzyme complex were investigated using molecular docking and molecular dynamics simulation studies, respectively. In vitro and in silico studies suggest two important structure-activity relationship (SAR) points that at least one azole ring is essential, and if there is approximately 8.0 ± 0.5 Å distance between the H-bond rich zone of ligand and the heteroaryl ring system of ligand has a major impact on aromatase inhibitory activity. Compounds with small group substitution on thiazole are found potentially may be used for the treatment of anti-breast cancer orally.Communicated by Ramaswamy H. Sarma.

In recent studies, monoamine oxidase (MAO) inhibitory effects of various thiazolylhydrazone derivatives have been demonstrated. Within the scope of this study, 12 new compounds containing thiazolylhydrazone groups were synthesized. The structures of the obtained compounds were elucidated by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry (HRMS) methods. The inhibitory effects of the final compounds on MAO enzymes were investigated by means of in vitro methods. In addition to enzyme inhibition studies, enzyme kinetic studies of compounds with high inhibitory activity were examined, and their effects on substrate-enzyme relations were investigated. Additionaly, cytotoxicity tests were carried out to determine the toxicities of the selected compounds, and the compounds were found to be nontoxic. The interactions of the active compound with the active site of the enzyme were characterized by in silico methods., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

This study delves into the intricate dynamics of the inflammatory response, unraveling the pivotal role played by cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2 subtypes. Motivated by the pursuit of advancing scientific knowledge, our contribution to this field is marked by the design and synthesis of novel pyrrole derivatives. Crafted as potential inhibitors of COX-1 and COX-2 enzymes, our goal was to unearth molecules with heightened efficacy in modulating enzyme activity. A meticulous exploration of a synthesis library, housing around 3000 compounds, expedited the identification of potent candidates. Employing advanced docking studies and field-based Quantitative Structure-Activity Relationship (FB-QSAR) analyses enriched our understanding of the complex interactions between synthesized compounds and COX enzymes. Guided by FB-QSAR insights, our synthesis path led to the identification of compounds 4g, 4h, 4l, and 4k as potent COX-2 inhibitors, surpassing COX-1 efficacy. Conversely, compounds 5b and 5e exhibited heightened inhibitory activity against COX-1 relative to COX-2. The utilization of pyrrole derivatives as COX enzyme inhibitors holds promise for groundbreaking advancements in the domain of anti-inflammatory therapeutics, presenting avenues for innovative pharmaceutical exploration., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Infectious diseases are a major concern around the world. Today, it is an urgent need for new chemotherapeutics for infectious diseases. Because of that, our group designed, synthesized, and analyzed 14 new quinoline derivatives endowed with the pharmacophore moiety of fluoroquinolones primarily for their antimicrobial effects. Their cytotoxicity effects were tested against six bacterial and four fungal strains and NIH/3T3 cell line. Additionally, their action mechanisms were evaluated against DNA gyrase and lanosterol 14α-demethylase (LMD). Furthermore, to eliminate the potential side effects, the active compounds were evaluated against the aromatase enzyme. The experimental enzymatic results were evaluated for active compounds' binding modes using molecular docking and molecular dynamics simulation studies. The results were utilized to clarify the structure-activity relationship (SAR). Finally, compound 4m was the most potent compound for its antifungal activity with low cytotoxicity against healthy cells and fewer possible side effects, while compounds 4j and 4l can be used alone for special patients who are suffering from fungal infections in addition to the primer disease., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Aim: Design of 5-methoxy benzofuran hybrids with 2-carbohydrazide and 2-(1,3,4-oxadiazol-2-yl) as potential inhibitors of monoamine oxidase (MAO)-B targeting Parkinson disease. Materials and methods: 12 compounds were synthesized and analyzed via high-resolution mass spectrometry, 1 H nuclear magnetic resonance and 13 C nuclear magnetic resonance techniques. In vitro fluorometric assay was used to investigate the activity of the synthesized compounds on both MAO-A and MAO-B isozymes. Results: Three compounds - 3a , 3c and 3e - displayed half maximal inhibitory concentration values of 0.051 ± 0.002, 0.038 ± 0.001 and 0.077 ± 0.003 μM in the inhibition of MAO-A and 0.048 ± 0.002, 0.040 ± 0.001 and 0.072 ± 0.002 μM for MAO-B, respectively. A molecular dynamics simulation study showed that compound 3c has poor stability as a complex with MAO-A. Conclusion: Compound 3c may be a potential candidate for the treatment of Parkinson disease.

Monoamine oxidases (MAOs) have become promising drug targets for the development of central nervous system agents. In recent research, it was shown that numerous piperazine derivatives exhibit hMAO inhibitory activity. Therefore, in this study, a novel series of 1,2,4-triazole-piperazine derivatives (5a-j) were designed, synthesized, characterized, and screened for their hMAO-A and hMAO-B inhibitory activities. When the ADME predictions were examined, it was seen that the pharmacokinetic profiles of all synthesized compounds were appropriate. Compounds 5a, 5b, 5c, and 5e, with H, F, Cl, and NO 2 groups on the 4-position of the phenyl ring, respectively, showed important MAO-A inhibitory activity. Compound 5c was found to be the most effective agent among the synthesized compounds with an IC 50 value of 0.070 ± 0.002 µM against the MAO-A enzyme. The synthesized compounds appear to support the results of other studies to design MAO inhibitors to obtain more suitable drugs, especially for neurological disorders such as depression and anxiety., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although radical treatment of Alzheimer's and Parkinson's disease is not possible yet, it is aimed to slow the course of the disease and increase the life quality of individuals with the drugs used in the clinic at the present time. Successful results have been achieved in the use of cholinesterase inhibitors and monoamine oxidase inhibitors together in these neurodegenerative diseases. In this study, indane ring which are in the structure of anticholinesterase effective molecules and 2-hydrazinothiazole structure whose inhibitory activities reported on monoamine oxidase-B (MAO-B) were combined; 4-(substituted phenyl)-2-[2-(3-phenyl-2,3-dihydro-1 H -inden-1-ylidene) hydrazinyl]thiazole derivatives ( 3a-3i ) were synthesized as dual inhibitors. The structures of the compounds were verified by IR, 1 H-NMR, 13 C-NMR, and HRMS spectroscopy. When enzyme inhibition activities were evaluated, it was determined that the compounds 3a (42.33%) and 3d (42.39%) on acetylcholinesterase (AChE) enzyme; compounds 3g (75.42%) and 3h (60.33%) showed inhibition on MAO-B enzyme at most, at 10 -3  M concentration., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

The synthesis of new N-(5-substituted-1,3,4-thiadiazol-2-yl)-2-[(5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio]acetamide derivatives and investigation of their anticancer activities were the aims of this work. All the new compounds' structures were elucidated by elemental analyses, IR, 1H NMR, 13C NMR and MS spectral data. Anticancer activity studies of the compounds were evaluated against MCF-7 and A549 tumor cell lines. In addition, with the purpose of determining the selectivity of cytotoxic activities, the most active compound was screened against a noncancer NIH3T3 cell line (mouse embryonic fibroblast cells). Among the tested compounds, compound 4y (N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-((5-(p-tolylamino)-1,3,4-thiadiazol-2-yl)thio)acetamide), showed promising cytotoxic activity against MCF7 cancer cell with an IC 50value of 0.084 ± 0.020 mmol L-1 and against A549 cancer cell with IC 50 value of 0.034 ± 0.008 mmol L-1, compared with cisplatin. The aromatase inhibitory activity was evaluated for compound 4y on MCF-7 cell line showing promising activity with IC50 of 0.062 ± 0.004 mmol L-1.

In the present study, a new series of 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-substituted piperazine-1-carbodithioate derivatives (2a-n) were synthesized and screened for their monoamine oxidase A and B inhibitory activity. The structures of compounds were elucidated using spectroscopic methods and some physicochemical properties of new compounds were predicted using Molinspiration and MolSoft programs. Compounds 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-(4-nitrophenyl)piperazine-1-carbodithioate (2j) and 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-2-oxoethyl 4-benzhydrylpiperazine-1-carbodithioate (2m) exhibited selective MAO-A inhibitory activity with IC 50  =   23.10, 24.14 µM, respectively. Some of the biological results were found in accordance with the obtained in silico data based on Lipinski's fule of five.