Synthesis, characterization, biological evaluation and in silico studies of novel 1,3,4-thiadiazole derivatives as aromatase inhibitors

• Published in: Journal of molecular structure Vol. 1296; p. 136903
• Main Authors: Demiraran, Sena, Osmaniye, Derya, Özkay, Yusuf, Kaplancıklı, Zafer Asım, Koçyiğit-Kaymakçıoğlu, Bedia, Tok, Fatih
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.01.2024
• Subjects: Aromatase; HSQC; MCF-7; NIH3T3 and molecular docking; Thiadiazole; HSQC; NIH3T3 and molecular docking; Aromatase; MCF-7; Thiadiazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.136903

•A new series of 1,3,4-thiadiazole derivatives were synthesized and characterized.•The in vitro anticancer activity of compounds were tested against MCF-7 and NIH3T3 cells.•The compounds were evaluated as inhibitors of aromatase enzyme using letrazole reference.•Docking studies were performed using crystal structures of aromatase enzyme.•A good ADME profile were predicted for all the compounds. In this study, some new thiosemicarbazide and their corresponding 1,3,4-thiadiazole derivatives containing pyridine nuclei were synthesized. Their structures were established based on FT-IR, 1HNMR , 13CNMR , 2D-NMR (HSQC) spectral data and elemental analysis. The MCF-7 and NIH3T3 cells were used to test the compound's anticancer effects. Among the compounds; 4a, 4b, 4d and 4g showed the most potent cytotoxic activity against MCF-7 at IC50 of 3.102±0.096 μM, 8.737±0.103 μM, 11.190±0.088 μM and 12.630±0.101 μM, respectively.Their inhibitory activity was assessed against the in vitro aromatase enzyme. Compounds 4a, 4b, 4d and 4g exhibited the promising aromatase inhibition activity with IC50 value of 0.027±0.002 µM, 0.068±0.005 µM, 1.456±0.009 µM and 3.316±0.001 µM, respectively (the standard drug letrazole has an IC50 value of 0.023±0.002 μM). The molecular docking studies were used to identify the key molecular interactions between the compounds 4a, 4b, 4d and 4g and the aromatase enzyme. Additionally, the physicochemical, druglikeness and pharmacokinetic properties of compounds were also evaluated. [Display omitted]