Design, synthesis, and biological investigation of new thiazole-based derivatives as multi-targeted inhibitors endowed with antiproliferative, antioxidant, and antibacterial properties.

INTRODUCTION

A novel series of thiazole-based derivatives and was developed, synthesized, and tested for antiproliferative activity as dual EGFR/VEGFR-2 inhibitors, antioxidants, and antibacterial agents.

METHODS

The structures of the new compounds and were validated using NMR spectroscopy and elemental microanalysis. The antiproliferative activity of and was tested against a panel of four cancer cell lines using MTT assay.

RESULTS AND DISCUSSION

Compounds and had the highest antiproliferative activity, with GI values of 30 and 27 nM, respectively, making them more potent than erlotinib (GI = 33 nM). Inhibitory studies for EGFR and VEGFR-2 demonstrated that compounds and were the most potent derivatives with dual inhibitory activity. Furthermore, compounds and exhibited significant antioxidant activity at 10 μM, with radical scavenging activity of 71% and 73%, respectively, compared to the reference Trolox (78%). Moreover, compounds and exhibit significant inhibitory activity against DNA gyrase, with compounds , , and displaying the highest inhibitory efficacy, yielding IC values of 182, 190, and 197 nM, respectively, in comparison to the reference novobiocin (IC = 170 nM). Compounds and have significant antibacterial efficacy against both Gram-positive and Gram-negative bacterial strains, as demonstrated by a twofold serial dilution experiment. They exhibit similar efficacy against , and , demonstrating more potency than ciprofloxacin, however displaying reduced effectiveness against compared to ciprofloxacin.