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

Compounds <b>11d</b> and <b>11f</b> had the highest antiproliferative activity, with GI₅₀ values of 30 and 27 nM, respectively, making them more potent than erlotinib (GI₅₀ = 33 nM). Inhibitory studies for EGFR and VEGFR-2 demonstrated that compounds <b>11d</b> and <b>11f</b> were the most potent derivatives with dual inhibitory activity. Furthermore, compounds <b>11d</b> and <b>11f</b> exhibited significant antioxidant activity at 10 μM, with radical scavenging activity of 71% and 73%, respectively, compared to the reference Trolox (78%). Moreover, compounds <b>11a-f</b> and <b>12a-f</b> exhibit significant inhibitory activity against <i>E. coli</i> DNA gyrase, with compounds <b>11b</b>, <b>11e</b>, and <b>12b</b> displaying the highest inhibitory efficacy, yielding IC₅₀ values of 182, 190, and 197 nM, respectively, in comparison to the reference novobiocin (IC₅₀ = 170 nM). Compounds <b>11b</b> and <b>11e</b> 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 <i>S. aureus, E. coli</i>, and <i>P. aeruginosa</i>, demonstrating more potency than ciprofloxacin, however displaying reduced effectiveness against <i>B. subtilis</i> compared to ciprofloxacin.