Abstract
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.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimalarials / chemical synthesis
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Antimalarials / chemistry*
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Antimalarials / pharmacology
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Hydrazones / chemical synthesis
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Hydrazones / chemistry*
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Hydrazones / pharmacology
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / enzymology*
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Protozoan Proteins / antagonists & inhibitors*
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Protozoan Proteins / metabolism
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Serine Proteinase Inhibitors / chemical synthesis
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Serine Proteinase Inhibitors / chemistry*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Subtilisins / antagonists & inhibitors*
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Subtilisins / metabolism
Substances
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Antimalarials
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Hydrazones
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Protozoan Proteins
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Quinolines
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Serine Proteinase Inhibitors
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Subtilisins
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subtilisin-like protease 1, Plasmodium falciparum