Synthesis, anticancer, and docking of new thiadiazolyl-triazole analogues hybridized with thiazolidinone/thiophene

The synthetic protocol of thiadiazole-triazole-thiazolidinone hybrids 6 and 7a-c is based on chloroacety-lation of the precursor thiadiazole-triazole analogue 4 followed by cyclization the produced 5-(2-chloroacetamido)-2-phenyl-N-(1,3,4-thiadiazol-2-yl)-2H-1,2,3-triazole-4-carboxamide compound 5 with ammonium thiocyanate. The introduction of thiophene ring system into the thiadiazole-triazole ana-logue is achieved by heterocyclizing the key chloroacetamide 5 with various thiocarbamoyl reagents 8 and 10 to yield the corresponding thiadiazole-triazole-thiophene hybrids 9 and 11, respectively. Further, in vitro MTT cytotoxic screening against four dissimilar cell lines, including HepG2, MCF-7, PC3, and Hep-2 was assessed in comparison to the reference drug 5-Fu. The outcomes demonstrated varying efficacy against cancer cell lines, displaying cytotoxic selectivity for MCF-7 and HepG-2. Thiadiazole-triazole hy-brids 7a-c, 9a, 9b, 11a, and 11b were discovered to be the most effective drugs against MCF-7 and HepG-2 cancer cells among these derivatives. Where, hybrid 7c displayed most potent IC50 values 11.62 +/- 0.43 and 9.25 +/- 0.37 mu M against MCF-7 and HepG-2, respectively. Additionally, investigations of the structure-activity relationship (SAR) helped to explain the origin of several powerful activities. The cytotoxic ac-tivities of the investigated compounds were good, with an IC50 range of 11.62 +/- 0.43-24.17 +/- 0.15 mu M. The crystal structure of the 5YJB protein, which was found in PDB, was docked with the generated thiadiazole-triazole hybrids to predict the types of interactions.(c) 2023 Elsevier B.V. All rights reserved.

Automated summary

The study synthesized a series of thiadiazole-triazole-thiazolidinone hybrids and evaluated their cytotoxicity against various cancer cell lines. The compounds with the most potent activity were identified, and the structure-activity relationship was analyzed to explain their anticancer efficacy.