文档介绍：From Antifungal Drug Target to New Candidate Drug: Molecular Modeling, Chemical Synthesis and Site-directed Mutagenesis
SHENG Chun-quan, ZHANG Wan-nian* To whom correspondence should be addressed. Phone: 86-21-25074460. Fax: 86-21-25074460. E-mail: ******@.
(School of Pharmacy, Military Key Laboratory of Medicinal Chemistry, Second Military Medical University, 325 Guohe Road, Shanghai 200433)
During the past two decades, the life threatening infections caused by pathogenic fungi have e mon, especially in individuals with promised hosts, such as patients undergoing anticancer chemotherapy an transplants and patients with AIDS. Clinically, candidosis, aspergillosis and osis are three major fungal infections in promised individuals. Moreover, dermatomycoses, such as toenails and tinea pedis, are among the most widespread human superficial and cutaneous fungal infections. However, the current antifungal therapy suffers from drug related toxicity, severe drug resistance, non-optimal ics and serious drug-drug interactions. Therefore, there is an emergent need to develop novel antifungal drugs with higher efficiency, broader-spectrum and lower toxicity.
1. The Binding mode of Azole Antifungal Agents with CACYP51
Lanosterol 14a-demethylase (CYP51) is the primary target of azole antifungal agents. In the present study, we constructed a 3D model of CYP51 from Candida albicans (CA