Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-<i>Plasmodium</i> activity.

ABSTRACT: Plasmodium falciparum HKMTs (PfHKMTs) play a key role in controlling Plasmodium gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in in vivo models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host versus parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent ant

SUBMITTER: Sundriyal S 

PROVIDER: S-EPMC5708365 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature