Author/Editor     Berne, Sabina; Podobnik, Barbara; Zupanec, Neja; Novak, Metka; Kraševec, Nada; Turk, Samo; Korošec, Branka; Lah, Ljerka; Šuligoj, Erika; Stojan, Jure; Gobec, Stanislav; Komel, Radovan
Title     Virtual screening yields inhibitors of novel antifungal drug target, benzoate 4-monooxygenase
Type     članek
Source     J Chem Inf Model
Publication year     2012
ISSN     1549-9596
Language     eng
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. Based on combined results, we selected 3-methyl-4-(1H-pyrrol-1-yl)benzoic acid (compound 2) as the best candidate for hit-to-lead follow-up in the antifungal drug discovery process.
Descriptors     ASCOMYCETES
ANTIFUNGAL AGENTS
CYTOCHROME P-450
LANOSTEROL
OXIDOREDUCTASES
BENZOATES
BINDING SITES
SPECTRUM ANALYSIS
COMPUTER SIMULATION