Design, synthesis and molecular modeling studies of thiosemicarbazide & thiazolyl-hydrazone derivatives as potential anticancer agents and topoisomerase inhibitors

• Published in: Journal of molecular structure 2024-04, Vol.1302, p.137488, Article 137488
• Main Authors: Şenkardeş, Sevil, Bolat, İrfan, Şahinbey, Hazal, Karakuş, Sevgi, Erdoğan, Ömer, Cantürk, Pakize, Özgüven, Serap Yılmaz, Çevik, Özge
• Format: Article
• Language: English
• Subjects: Anticancer; Docking study; Thiazole; Thiosemicarbazide; Topoisomerase
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.137488

•Thiosemicarbazide and thiazolyl-hydrazone derivatives were synthesized as potential anticancer agents.•The cytotoxic activity was tested against SH-SY5Y neuroblastoma and NIH-3T3 normal cell lines.•Apoptosis assay were reported.•DNA topoisomerase-I and II were studied.•Molecular docking studies were performed. This study involved the design, synthesis and evaluation of a series of novel thiosemicarbazide and thiazolyl-hydrazone derivatives. The synthesized compounds were tested for cytotoxic effects SH-SY5Y neuroblastoma cells, as well as NIH-3T3 normal cell line using the MTT assay. Among the tested compounds, 3b, 3d, 3i, 4b, 4d and 4i exhibited IC50 values ranging from 1.97 µM to 3.22 µM in the SH-SY5Y cancer cell line with lower cytotoxicity toward NIH-3T3 cells. Moreover, all compounds were also screened for their topoisomerase I and II inhibitory activity and compound 3b completely inhibited the topoisomerase I enzyme, whereas all compounds showed potent topoisomerase II inhibitory activity. Docking studies were performed to identify the mode of binding of the tested compounds to the active site of topoisomerase I and II. In conclusion, N-(4-(2-((2-chlorophenyl)carbamothioyl)hydrazine-1-carbonyl)phenyl)benzamide (3b) emerges as a promising inhibitor of topoisomerase I and II and holds potential as a lead compound in the quest for novel anticancer agents.