ISATIN/THIOSEMICARBOHYDRAZONE HYBRIDS: FACILE SYNTHESIS, AND THEIR EVALUATION AS ANTI-PROLIFERATIVE AGENTS AND METABOLIC ENZYME INHIBITORS

Yakan H., Azam M., Kansiz S., Muglu H., Erguel M., Taslimi P., ...Daha Fazla

BULLETIN OF THE CHEMICAL SOCIETY OF ETHIOPIA, cilt.37, sa.5, ss.1221-1236, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37 Sayı: 5
  • Basım Tarihi: 2023
  • Doi Numarası: 10.4314/bcse.v37i5.14
  • Dergi Adı: BULLETIN OF THE CHEMICAL SOCIETY OF ETHIOPIA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, Veterinary Science Database, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1221-1236
  • Anahtar Kelimeler: Isatin, Thiosemicarbazone, Anti-proliferative activity, Enzyme inhibition, Molecular docking
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

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 & mu;M and 23.41 & mu;M, respectively. In addition, the compounds (1-6) inhibited the hCA I and II, their Ki values 2.01 & PLUSMN; 0.35 - 21.55 & PLUSMN; 2.56 and 1.24 & PLUSMN; 0.33 - 25.03 & PLUSMN; 5.48 & mu;M, respectively. AChE was also successfully inhibited by these compounds (1-6), with Ki values ranging from 40.37 & PLUSMN; 8.23 to 125.43 & PLUSMN; 24.93 & mu;M. The best Ki values for 3, 6, and 4 for & alpha;-glycosidase were 564.35 & PLUSMN; 72.06, 594.38 & PLUSMN; 52.04, and 683.437 & PLUSMN; 66.58 & mu;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.