Identification of hydroxyphenyl cyanovinyl thiazoles as new structural scaffold of potential antibacterial agents

Unique hydroxyphenyl cyanovinyl thiazoles (HCTs) as new structural scaffolds of potential antibacterial agents were developed to overcome global increasingly serious drug resistance. Some synthesized HCTs could suppress the growth of the tested strains, especially, benzothiophenyl HCT 5c exhibited superior anti-Escherichia coli activity with a lower MIC of 0.5 μg/mL to norfloxacin (MIC = 1 μg/mL). The active benzothiophenyl HCT 5c displayed no obvious hemolysis, low cytotoxicity and a much lower trend for the development of drug-resistance than norfloxacin. Further exploration revealed that benzothiophenyl HCT 5c could intercalate to DNA to form a DNA-5c complex, which disturbed the biological functions to facilitate bacterial death. ADME analysis indicated that compound 5c possessed favorable druggability and promising pharmacokinetic properties. This work provided an insight into further developing hydroxyphenyl cyanovinyl thiazoles as new structural scaffold of promising antibacterial candidates.