Resistance to antimalarial drugs has spread rapidly over the past few decades. There aren't effective alternatives to artemisinin for the treatment of resistant P. falciparum malaria. In 2016, artemisinin resistance has been confirmed in 5 countries of the Greater Mekong subregion. Artemisinin-based combination therapies (ACTs) recommended by WHO are life-saving in areas of high resistance. Previous studies demonstrate the implication of Syk protein (spleen tyrosine kinase) in a mechanism of infection of RBCs by parasites . Syk protein is present in human erythrocytes and RBCs membrane protein band 3 is its major target following his activation by oxidant stress. Tyr phosphorylation of band 3 occurs during P. falciparum growth leading to the release of microparticles containing hemicromes and structural weakening of the host cell membrane. Syk inhibitors block these events interacting with Syk protein catalytic site. Our study is focused on three Syk inhibitors Gleevec, Syk II and R406 as promising antimalarial drugs and we have performed and compared the results of proteomics and in silico studies.
In vitro studies and computational analysis of Syk inhibitors as new antimalarial drugs
R Dallocchio;
2017
Abstract
Resistance to antimalarial drugs has spread rapidly over the past few decades. There aren't effective alternatives to artemisinin for the treatment of resistant P. falciparum malaria. In 2016, artemisinin resistance has been confirmed in 5 countries of the Greater Mekong subregion. Artemisinin-based combination therapies (ACTs) recommended by WHO are life-saving in areas of high resistance. Previous studies demonstrate the implication of Syk protein (spleen tyrosine kinase) in a mechanism of infection of RBCs by parasites . Syk protein is present in human erythrocytes and RBCs membrane protein band 3 is its major target following his activation by oxidant stress. Tyr phosphorylation of band 3 occurs during P. falciparum growth leading to the release of microparticles containing hemicromes and structural weakening of the host cell membrane. Syk inhibitors block these events interacting with Syk protein catalytic site. Our study is focused on three Syk inhibitors Gleevec, Syk II and R406 as promising antimalarial drugs and we have performed and compared the results of proteomics and in silico studies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
