Design, synthesis, in vitro biological assessment and in silico molecular modeling study of thiazole-thiazolidinone derivatives as potent anti-cancer agents
Shoaib Khan, Hayat Ullah, Rafaqat Hussain, Misbah Khan, Yousaf Khan, Amjad Hussain, Tayyiaba Iqbal, Hamid Ali, Rashid Iqbal, Muhammad Irfan Akram, Saeedah Musaed Almutairi
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.