Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicumReport as inadecuate


Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum


Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum - Download this document for free, or read online. Document in PDF available to download.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Science, Central China Normal University, Wuhan 430079, China



These authors contributed equally to this work.





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Academic Editors: Antonio Trincone and Keith B. Glaser

Abstract Sterol 14α-demethylases from Cytochrome P450 family CYP51s are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from Penicillium italicum PiCYP51A was constructed through homology modeling based on the crystal structure of human CYP51A PDB: 3LD6. Molecular dynamics MD simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors DMIs, pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC50 values to P. italicum isolates. The results could provide references for de novo antifungal drug design. View Full-Text

Keywords: Penicillium italicum; PiCYP51A; pharmacophore; demethylase inhibitors; virtual screening; molecular docking Penicillium italicum; PiCYP51A; pharmacophore; demethylase inhibitors; virtual screening; molecular docking





Author: Yongze Yuan †, Rui Han †, Qianwen Cao, Jinhui Yu, Jiali Mao, Tingfu Zhang, Shengqiang Wang, Yuhui Niu and Deli Liu *

Source: http://mdpi.com/



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