Virtual Screening Yields
Inhibitors of Novel Antifungal
Drug Target, Benzoate 4‑Monooxygenase
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Abstract
Fungal CYP53 enzymes are highly conserved proteins, involved
in
phenolic detoxification, and have no homologues in higher eukaryotes,
rendering them favorable drug targets. Aiming to discover novel CYP53
inhibitors, we employed two parallel virtual screening protocols and
evaluated highest scoring hit compounds by analyzing the spectral
binding interactions, by surveying the antifungal activity, and assessing
the inhibition of catalytic activity. On the basis of combined results,
we selected 3-methyl-4-(1H-pyrrol-1-yl)benzoic acid (compound <b>2</b>) as the best candidate for hit-to-lead follow-up in the
antifungal drug discovery process