Isatin/thiosemicarbohydrazone hybrids: Facile synthesis, and their evaluation as anti-proliferatıve agents and metabolıc enzyme inhibitors
Hasan Yakan, Mohammed Afzal Azam, Sevgi Kansız, Halit Muğlu, Mustafa Ergül, Parham Taslımı, Ümit M. Koçyiğit, Muhammet Karaman, Saud I. Al‐Resayes, Min Kim
Abstract
ABSTRACT. We are reporting a novel series of thiosemicarbazone derivatives derived from isatin (1-6), structural determination, and investigation of the inhibitory properties against proliferative, carbonic anhydrase, and cholinesterase enzymes. The anti-proliferative effects of the compounds were measured by XTT assay against MCF-7 and MDA-MB-231 cancerous cell lines. Compound 3 showed significant cytotoxic effects on both MCF-7 and MDA-MB-231 cell lines, with IC50 values of 8.19 μM and 23.41 μM, respectively. In addition, the compounds (1-6) inhibited the hCA I and II, their Ki values 2.01 ± 0.35 – 21.55 ± 2.56 and 1.24 ± 0.33 – 25.03 ± 5.48 µM, respectively. AChE was also successfully inhibited by these compounds (1-6), with Ki values ranging from 40.37 ± 8.23 to 125.43 ± 24.93 µM. The best Ki values for 3, 6, and 4 for α-glycosidase were 564.35 ± 72.06, 594.38 ± 52.04, and 683.437 ± 66.58 µM, respectively. Binding affinities were determined to be -6.697 kcal/mol, -8.251 kcal/mol, -9.932 kcal/mol, and -4.946 kcal/mol for hCA I, hCA II, AChE, and α-glucosidase enzymes, respectively. These findings reveal that the formed compounds containing isatin moieties were crucial in the enzyme inhibition. KEY WORDS: Isatin, Thiosemicarbazone, Anti-proliferative activity, Enzyme inhibition, Molecular docking Bull. Chem. Soc. Ethiop. 2023, 37(5), 1221-1236. DOI: https://dx.doi.org/10.4314/bcse.v37i5.14