Synthesis of Novel Urea and Sulfonamide Derivatives of Isatin Schiff Bases as Potential Anti-cancer Agents

Demirel U. U., ÖLGEN S., Karaman E. F., Tanol M., Ozden S., GÖKER A. H.

LETTERS IN DRUG DESIGN & DISCOVERY, vol.19, no.9, pp.847-857, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 9
  • Publication Date: 2022
  • Doi Number: 10.2174/1570180819666220224115908
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE
  • Page Numbers: pp.847-857
  • Keywords: Urea and sulfonamide derivatives, isatin, schiff bases, cytotoxicity, ADME prediction, synthesis, molecular docking, DRUG-METABOLISM, IN-VITRO, INHIBITORS, DESIGN
  • Istanbul University Affiliated: Yes


Background: Among the many types of chemical scaffolds, isatin derivatives, including their Schiff bases, have been extensively studied to find novel therapeutic agents against cancer. Amide or urea groups containing derivatives were also discovered to be tyrosine kinase inhibitors. Objective: This study aims to find potent compounds by designing 16 novel urea and sulfonamide derivatives of isatin Schiff bases. Methods: Compounds were tested against PC-3, HepG2, SH-SY5Y, A549 cancerous, and NIH/3T3 non-cancerous cell lines using cell culture assay. Results: Among the tested compounds 7a, 7b, 7c, 7d, 7h, 8a, and 8f presented potential inhibitions against cellular proliferation activities of HepG2 cells with average IC50 values of 31.97, 42.13, 31.50, 47.98, 32.59, 43.44, and 37.81 mu M, respectively. They showed better inhibition potencies than the reference compound doxorubicin, and its value was measured as 51.15 mu M in the same culture assay. The cytotoxic activities of the compounds in other cell lines were found to be less potent compared to doxorubicin. Conclusion: In vitro experiments demonstrated that designed compounds have the first evidence that they might be active against hepatocellular carcinoma. According to ADME prediction results, all compounds presented drug-like and good metabolic properties.