Quinolylhydrazones as novel inhibitors of Plasmodium falciparum serine protease PfSUB1.
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.
European Research Centre for Drug Discovery and Development (NatSynDrugs), University of Siena, Via A. Moro, 53100 Siena, Italy.
Sandra
S
Gemma
Simone
S
Giovani
Margherita
M
Brindisi
Pierangela
P
Tripaldi
Simone
S
Brogi
Luisa
L
Savini
Isabella
I
Fiorini
Ettore
E
Novellino
Stefania
S
Butini
Giuseppe
G
Campiani
Maria
M
Penzo
Michael J
MJ
Blackman
D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013381:Subtilisins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000962:Antimalarials; D006835:Hydrazones; D015800:Protozoan Proteins; D011804:Quinolines; D015842:Serine Proteinase Inhibitors; D013381:Subtilisins; C403176:subtilisin-like protease 1, Plasmodium falciparum