Determination of biological studies and molecular docking calculations of isatin-thiosemicarbazone hybrid compounds

Design, synthesis, structural elucidation, and investigation of cytotoxic and antimicrobial activity, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzyme inhibition effects of isatinthiosemicarbazone hybrid compounds (1–15) are reported in this study. Hybrid compounds (14 and 15) were synthesized, isolated, and characterized for the first time. FT-IR, 1H NMR, and 13C NMR spectroscopic methods and elemental analysis were used to characterize the structures of the compounds. In the enzymatic evaluation, hybrid compound 13 was observed as the most potent inhibitor of AChE with a K˙ I value of 0.94 ± 0.13 μM (all compound K˙ I values between 0.94 ± 0.13 and 4.47 ± 0.92), also this compound was observed as the most potent inhibitor of BChE with a K˙ I value of 0.82 ± 0.11 μM (all compounds had K˙ I values between of 0.82 ± 0.11 and 3.48 ± 0.92). Almost all compounds were shown better inhibition profile than standard compound. In the theoretical calculations, the comparison of the biological activities of isatin-thiosemicarbazone hybrid derivatives against enzymes was studied. The enzymes studied in docking calculations are AChE and BChE. Then, ADME/T analysis was conducted to examine the drug properties of these derivatives. Besides, the antimicrobial activity of these molecules was investigated by the microdilution method according to Clinical Laboratory Standards Institute (CLSI) criteria in the study. Cytotoxic activity of isatin-thiosemicarbazone hybrids was determined by the XTT cell viability assay on human breast cancer cell lines MCF-7 and MDA-MB-231. Among the hybrid compounds, compound 8 exhibited the most potent cytotoxic activity with IC50 values of 23.42 ± 0.21 μg/mL and 19.68 ± 0.23 μg/mL on MCF-7 and MDA-MB-231 cell lines, respectively. Overall, the hybridization of isatin and thiose