Quinolylhydrazones as novel inhibitors of Plasmodium falciparum serine protease PfSUB1
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- 作者：S ; ra Gemma ; Simone Giovani ; Margherita Brindisi ; Pierangela Tripaldi ; Simone Brogi ; Luisa Savini ; Isabella Fiorini ; Ettore Novellino ; Stefania Butini ; Giuseppe Campiani ; Maria Penzo ; Michael J. Blackman
- 关键词：Malaria ; Egress ; Serine protease inhibitors ; PfSUB1 ; Hydrazones
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：15 August, 2012
- 年：2012
- 卷：22
- 期：16
- 页码：5317-5321
- 全文大小：510 K
文摘
Plasmodium falciparum subtilisin-like protease 1 (PfSUB1) is a serine protease that plays key roles in the egress of the parasite from red blood cells and in preparing the released merozoites for the subsequent invasion of new erythrocytes. The development of potent and selective PfSUB1 inhibitors could pave the way to the discovery of potential antimalarial drugs endowed with an innovative mode of action and consequently able to overcome the current problems of resistance to established chemotherapies. Through the screening of a proprietary library of compounds against PfSUB1, we identified hydrazone 2 as a hit compound. Here we report a preliminary investigation of the structure-activity relationships for a class of PfSUB1 inhibitors related to our identified hit.