Synthesis, molecular docking, and antiproliferative activity studies of bromine bearing Schiff bases

Abstract

Bromine-bearing compounds are found in a variety of natural products and synthetic drugs and exhibit a variety of biological activities. They often display particular properties such as enhanced stability, improved lipophilicity, and larger molecular interactions, making them valuable in drug design and development. In this study, three bromine-bearing Schiff bases were synthesized, characterized, and tested in lung (A549) and colon (DLD-1) cancer cell lines for 72 h incubation time. The results demonstrated that compounds had antiproliferative activity in screened cell lines. The compounds were also tested on a healthy embryonic kidney cell line (HEK-293T) to evaluate their toxic effects on non-cancerous cells. In vitro results of compounds interacting with the most suitable target were confirmed by in silico approaches. All bromine-containing compounds were interacted with the receptor tyrosine kinase FLT3 target via molecular docking. From the interaction results of the 6JQR crystal structure with 2-Br, the docking score value was calculated as −8.178 kcal/mol, and this value was determined to be better than the docking score (−7.269 kcal/mol) value of gilteritinib. Pharmacokinetics, toxicity properties and Lipinski violations of the compounds were estimated by ADMET and were calculated to be in the range of recommended values. Molecules demonstrated limited efficacy against A549 cells line, however; they exhibited relatively greater effectiveness against DLD-1 cell line. Notably, the IC₅₀ value of 2-Br was comparable to that of cisplatin. All molecules exhibited minimal toxicity.