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 | |
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 |