title: Design and synthesis of antifungal benzoheterocyclic derivatives by scaffold hopping.
abstract: The incidence of invasive fungal infections and associated mortality is increasing dramatically. Although azoles are first-line antifungal agents, cross-resistance and hepatic toxicity are their two major limitations. The discovery of novel non-azole lead compounds will be helpful to overcome these problems. On the basis of our previously reported benzopyran non-azole CYP51 inhibitor, scaffold hopping was used to design structurally diverse new compounds and expand the structure-activity relationships of the lead structure. Five kinds of scaffolds, namely benzimidazole, benzoxazole, benzothiazole, quinazolin-4-one and carboline, were chosen for synthesis. In vitro antifungal activity data and results from molecular docking revealed that the scaffold was important for the antifungal activity. Several compounds showed potent activity against both standard and clinically resistant fungal pathogens, suggesting that they can serve as a good starting point for the discovery of novel antifungal agents.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005658:Fungi / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D006571:Heterocyclic Compounds