Novel Thiazole Derivatives Containing Imidazole and Furan Scaffold: Design, Synthesis, Molecular Docking, Antibacterial, and Antioxidant Evaluation

Abstract

Carbothioamides <b>3a</b>,<b>b</b> were generated in high yield by reacting furan imidazolyl ketone <b>1</b> with <i>N</i>-arylthiosemicarbazide in EtOH with a catalytic amount of conc. HCl. The reaction of carbothioamides <b>3a</b>,<b>b</b> with hydrazonyl chlorides <b>4a</b>-<b>c</b> in EtOH with triethylamine at reflux produced 1,3-thiazole derivatives <b>6a</b>-<b>f</b>. In a different approach, the 1,3-thiazole derivatives <b>6b</b> and <b>6e</b> were produced by reacting <b>3a</b> and <b>3b</b> with chloroacetone to afford <b>8a</b> and <b>8b</b>, respectively, followed by diazotization with 4-methylbenzenediazonium chloride. The thiourea derivatives <b>3a</b> and <b>3b</b> then reacted with ethyl chloroacetate in ethanol with AcONa at reflux to give the thiazolidinone derivatives <b>10a</b> and <b>10b</b>. The produced compounds were tested for antioxidant and antibacterial properties. Using phosphomolybdate, promising thiazoles <b>3a</b> and <b>6a</b> showed the best antioxidant activities at 1962.48 and 2007.67 µgAAE/g dry samples, respectively. Thiazoles <b>3a</b> and <b>8a</b> had the highest antibacterial activity against <i>S. aureus</i> and <i>E. coli</i> with 28, 25 and 27, 28 mm, respectively. Thiazoles <b>3a</b> and <b>6d</b> had the best activity against <i>C. albicans</i> with 26 mm and 37 mm, respectively. Thiazole <b>6c</b> had the highest activity against <i>A. niger</i>, surpassing cyclohexamide. Most compounds demonstrated lower MIC values than neomycin against <i>E. coli</i>, <i>S. aureus</i> and <i>C. albicans</i>. A molecular docking study examined how antimicrobial compounds interact with DNA gyrase B crystal structures. The study found that all of the compounds had good binding energy to the enzymes and reacted similarly to the native inhibitor with the target DNA gyrase B enzymes' key amino acids.