Plasmepsin II inhibition and antiplasmodial activity of Primaquine-Statine 'double-drugs'

Sergio Romeo; Mario Dell'Agli; Silvia Parapini; Luca Rizzi; Germana Galli; Monica Mondani; Anna Sparatore; Donatella Taramelli; Enrica Bosisio

doi:10.1016/j.bmcl.2004.03.030

Plasmepsin II inhibition and antiplasmodial activity of Primaquine-Statine 'double-drugs'

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2931-4. doi: 10.1016/j.bmcl.2004.03.030.

Authors

Sergio Romeo¹, Mario Dell'Agli, Silvia Parapini, Luca Rizzi, Germana Galli, Monica Mondani, Anna Sparatore, Donatella Taramelli, Enrica Bosisio

Affiliation

¹ Institute of Medicinal Chemistry, University of Milan, Viale Abruzzi 42, 20131 Milan, Italy. sergio.romeo@unimi.it

PMID: 15125962
DOI: 10.1016/j.bmcl.2004.03.030

Abstract

Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the 'double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 microM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemistry*
Amino Acids / pharmacology
Animals
Antimalarials / chemical synthesis*
Antimalarials / pharmacology
Aspartic Acid Endopeptidases / antagonists & inhibitors*
Chloroquine
Cross-Linking Reagents
Drug Design
Drug Resistance
Erythrocytes / microbiology
Humans
Inhibitory Concentration 50
Plasmodium falciparum / drug effects*
Plasmodium falciparum / enzymology
Primaquine / chemistry*
Primaquine / pharmacology
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / pharmacology
Protozoan Proteins
Structure-Activity Relationship

Substances

Amino Acids
Antimalarials
Cross-Linking Reagents
Protease Inhibitors
Protozoan Proteins
Chloroquine
Aspartic Acid Endopeptidases
plasmepsin II
Primaquine
statine