Design, synthesis and biological activity of novel triazine inhibitors of Candida albicans secreted aspartic protease 2
10.16438/j.0513-4870.2020-0880
- VernacularTitle:新型三嗪类白念珠菌SAP2抑制剂的设计、合成和生物活性研究
- Author:
Ji YANG
1
;
Guo-qiang DONG
2
;
Na LIU
2
;
Chun-quan SHENG
3
Author Information
1. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China
3. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China
- Publication Type:Research Article
- Keywords:
triazine derivative;
SAP2 inhibitor;
virulence factor
- From:
Acta Pharmaceutica Sinica
2020;55(7):1647-1660
- CountryChina
- Language:Chinese
-
Abstract:
In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.
