ISATIN/THIOSEMICARBAZONE HYBRIDS: FACILE SYNTHESIS, AND THEIR EVALUATION AS ANTIPROLIFERATIVE AGENTS AND METABOLIC ENZYME INHIBITORS

• Published in: Bulletin of the Chemical Society of Ethiopia 2023-12, Vol.37 (5), p.1221
• Main Authors: Yakan, Hasan, Azam, Mohammed, Kansiz, Sevgi, Muglu, Halit, Ergul, Mustafa, Taslimi, Parham, Kocyigit, Umit M, Karaman, Muhammet, Al-Resayes, Saud I, Min, Kim
• Format: Article
• Language: English
• Subjects: Biopharmaceutics; Type 2 diabetes
• ISSN: 1011-3924
• DOI: 10.4314/bcse.v37i5.14

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 I[C.sub.50] values of 8.19 [micro]M and 23.41 [micro]M, respectively. In addition, the compounds (1-6) inhibited the hCA I and II, their [K.sub.i] values 2.01 [+ or -] 0.35 - 21.55 [+ or -] 2.56 and 1.24 [+ or -] 0.33 - 25.03 [+ or -] 5.48 [micro]M, respectively. AChE was also successfully inhibited by these compounds (1-6), with [K.sub.i] values ranging from 40.37 [+ or -] 8.23 to 125.43 [+ or -] 24.93 [micro]M. The best [K.sub.i] values for 3, 6, and 4 for [alpha]-glycosidase were 564.35 [+ or -] 72.06, 594.38 [+ or -] 52.04, and 683.437 [+ or -] 66.58 [micro]M, 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 [alpha]-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