Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo[2,1-b][1,3,4] thiadiazoles

A series of 2-(naphthalen-1-yl)-methyl-6-arylimidazo[2,1-b][1,3,4]thiadiazole derivatives was prepared and studied for cytotoxicity against murine leukemia L1210, human cervix carcinoma HeLa, and human T lymphocyte CEM cell lines. The preliminary study showed that compounds 5g, 6g, 7a-c, 7e, and 8e were more potent among the tested compounds. The pharmacokinetic properties of all compounds were then investigated with FAF-Drugs, a tool for prediction of ADME and toxicity. Finally, in order to support in vitro studies, molecular docking studies were performed by using AutoDock Vina with a Lamarckian genetic algorithm to determine whether or not the synthesized compounds could be used as inhibitors for the protein structure 1m17 (EGFR). The docking scores of many compounds were found to be higher than [6,7-bis(2-methoxy-ethoxy)quinazoline-4-yl]-(3-ethynyl phenyl)amine, an inhibitor of the 1m17 EGFR receptor. Among the selected compounds 7b, 7c, 7e, 7f, 7g, and 8g showed better stability in the molecular dynamics simulation study. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A series of derivatives of 2-(naphthalen-1-yl)-methyl-6-arylimidazo[2,1-b][1,3,4]thiadiazole were synthesized and studied for cytotoxicity against various cell lines. The pharmacokinetic properties of the compounds were evaluated using a prediction tool, and molecular docking studies were conducted to assess their potential as inhibitors for the EGFR protein structure. Selected compounds showed promising stability in molecular dynamics simulations.