Virtual Screening Yields Inhibitors of Novel Antifungal Drug Target, Benzoate 4-Monooxygenase
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- 作者：Sabina Berne ; Barbara Podobnik ; Neja Zupanec ; Metka Novak ; Nada Kra拧evec ; Samo Turk ; Branka Koro拧ec ; Ljerka Lah ; Erika 艩uligoj ; Jure Stojan ; Stanislav Gobec ; Radovan Komel
- 刊名：Journal of Chemical Information and Modeling
- 出版年：2012
- 出版时间：November 26, 2012
- 年：2012
- 卷：52
- 期：11
- 页码：3053-3063
- 全文大小：539K
- 年卷期：v.52,no.11(November 26, 2012)
- ISSN：1549-960X
文摘
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 2) as the best candidate for hit-to-lead follow-up in the antifungal drug discovery process.