Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors

Abstract

<div><p></p><p>In the present article, we describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile and molecular modelling evaluation. We found that one of the tested compounds, compound <b>7</b>, significantly inhibits activity of <i>Staphylococcus aureus</i> DNA gyrase with an IC₅₀ below 15 μM. Besides, this compound displays antibacterial activity on reference <i>Staphylococuss</i> spp. and <i>Enterococcus faecalis</i> strains as well as clinical <i>S. aureus</i> isolates at non-cytotoxic concentrations in mammalian cells with MIC values ranging from 16 to 32 μg/mL thereby indicating, in some cases, equipotent or even more effective action than standard drugs such as vancomycin, ampicillin and nitrofurantoin. The computational studies showed that both molecular geometry and the electron density distribution have a great impact on antibacterial activity of thiosemicarbazide derivatives.</p></div