Aim: Novel bacterial topoisomerase inhibitors (NBTIs) are a promising class of bacterial topoisomerase II inhibitors that are gaining more and more importance mainly because of their excellent antibacterial activity, as well as their lack of cross-resistance to quinolones. Results: Described here is the synthesis and biological evaluation of a tiny series of new virtually assembled NBTIs containing synthetically feasible right-hand side fragments capable of binding the GyrA subunit of the bacterial DNA gyrase-DNA complex. Conclusion: NBTI variants with incorporated 1-phenylpyrazole right-hand side moiety show suitable antibacterial activity against Gram-positive Staphylococcus aureus, with confirmed selectivity over the human topoisomerase IIα enzyme.
Keywords: DNA gyrase inhibitors; antibacterials; drug discovery; intercalators; novel bacterial topoisomerase inhibitors.