Design, synthesis, in vitro biological assessment and in silico molecular modeling study of thiazole-thiazolidinone derivatives as potent anti-cancer agents

Abstract

The current study addressed the synthesis of thiazole-based thiazolidinone derivatives (1–18) using stepwise reaction processes, and their structure was confirmed using various characterization techniques such as 1HNMR, 13CNMR, and HREI-MS. Furthermore, the biological features of these analogues as anti-cancer drugs against human cancer cell lines (HCC78 and H3122) were identified. Their inhibitory potentials were determined using the half-maximal inhibitory concentration (MIC50) in the presence of their standard drugs Tetrandrineb (IC50 = 10.70 ± 0.30 µM), respectively. Structure activity relationship (SAR) was established for all the synthesized scaffolds and compared their inhibitory potentials with standard, in which scaffolds 1 (IC50 = 5.20 ± 0.40 µM), 2 (IC50 = 4.10 ± 0.20 µM), 3 (IC50 = 6.30 ± 0.20 µM), 4 (IC50 = 8.90 ± 0.10 µM), 6 (IC50 = 8.10 ± 0.20 µM), 7 (IC50 = 8.70 ± 0.10 µM), 8 (IC50 = 3.90 ± 0.30 µM), 9 (IC50 = 2.10 ± 0.20 µM), 10 (IC50 = 3.30 ± 0.20 µM) and 16 (IC50 = 8.90 ± 0.20 µM) exhibited the most influential activity. These compounds were subsequently examined using molecular docking experiments, which evaluate the binding interactions of ligands with enzyme active sites.