Abstract
Exploring the structure-activity relationships (SAR) of a new set of phenylpyrazoles unveiled a potential anti-enterococcus lead compound 12. The benzofuran moiety linked to the phenylpyrazole 12 was 32 times better than vancomycin against Enterococcus faecalis ATCC 51299. Besides, compound 12 is expected to have an excellent oral bioavailability according to the in silico studies. Of SAR analysis, we found that the benzofuran side chain was essential for the activity. Changing the benzofuran with either benzothiophene, phenyl, pyridinyl, tolyl, or naphthyl reduces/nullifies the pharmacological action. Besides the anti-enterococcal activity, derivatives 4 and 6 can be used to develop new broad-spectrum antibiotics as they exhibited activity against the wild-type highly virulent Escherichia coli isolate. Moreover, compound 13 was proved to show antifungal activity (MIC = 4 mu g/ml) against the Candida albicans SS5314 (wild type). Finally, the in silico analysis showed that those compounds have good profiles regarding the absorption, distribution, metabolism, and excretion studies, drug-likeness and pharmacokinetics properties.