Sortase A (SrtA) is a membrane enzyme responsible for the covalent anchoring of surface proteins on the cell wall of Gram-positive bacteria. Nowadays, it is considered an interesting target for the development of new anti-infective drugs which aim to interfere with important Gram-positive virulence mechanisms. Along the years, we studied the anti-staphylococcal and anti-biofilm activity of some natural and synthetic polyhalogenated pyrrolic compounds, called pyrrolomycins. Some of them were active on Gram-positive pathogens at a μg/mL range of concentration (1.5–0.045 μg/mL) and showed a biofilm inhibition in the range of 50–80% [1,2,3].
We designed and synthesized novel pyrrolomycins, applying an efficient and easy-to-use microwave synthetic methodology. All compounds showed a good inhibitory activity toward SrtA, in accordance with the molecular modelling studies, having IC50 values ranging from 130 to 300 µM comparable to berberine hydrochloride. The best compound exhibits a high capability to interfere with biofilm formation of S. aureus with an IC50 in the nanomolar range. It is also effective in altering S. aureus murein hydrolase activity, responsible for degradation, turnover, and maturation of bacterial peptidoglycan [4]. In light of these encouraging results, herein we present our efforts in finding new effective agents able to inhibit biofilm formation.
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