Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as possible anticancer agents

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 healthy 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 IC50 value of 0.084 ± 0.020 mmol L–1 and against A549 cancer cell with IC50 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

Design, synthesis, molecular docking and molecular dynamic studies of novel benzimidazole-thiazole derivatives as potent and selective COX-2 inhibitors

A novel class of benzimidazole-thiazole products have been designed as potential inhibitors of cyclooxygenase, and the synthesized compound structures were verified using instrumental analysis techniques. The in vitro inhibitory effect on COX-1 was dose-dependent, with a significant reduction in effectiveness at lower concentrations. Among the compounds (7b) (IC50 0.297 μM) (7c) (IC50 0.311 μM) (8b) (IC50 0.279 μM) and (8c) (IC50 0.215 μM), which are the most active compounds, IC50 values were close to celecoxib (IC50 0.132 μM) against COX-2. Molecular docking studies were carried out on compounds against COX-2 using Glide XP. The compounds 7b, 7c, 8b, and 8c demonstrated significant docking scores of −8.927 kcal mol−1, −8.578 kcal mol−1, −8.485 kcal mol−1, and −8.899 kcal mol−1, respectively, which suggest a promising interaction with the COX-2 enzyme. Moreover, molecular dynamics simulations of 100 ns duration were performed with COX-2 and active compound complexes using Gromacs. The dynamic simulation results support the findings from the molecular docking studies and suggest that compounds 7b, 7c, 8b, and 8c may have the potential to act as potent and selective COX-2 inhibitors

Novel 1-(2-pyrimidin-2-yl)piperazine derivatives as selective monoamine oxidase (MAO)-A inhibitors

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 IC50 = 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

Novel oxadiazole-thiadiazole derivatives: synthesis, biological evaluation, and <i>in silico</i> studies

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 1H NMR, 13C 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</p

Synthesis and biological evaluation of novel 1,3,4-thiadiazole derivatives as possible anticancer agents

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 IC50value of 0.084 ± 0.020 mmol L−1 and against A549 cancer cell with IC50 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

New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a-h were characterized using 1H NMR, 13C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC50 value of 7.34 ± 0.21 μM and 4.56 ± 0.18 μM, respectively. These results were compared to standard drugs, doxorubicin (IC50 = 12.420 ± 0.5 μM) and Hoechst 33342 (IC50 = 0.422 ± 0.02 μM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (ΔE = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties