Figure 1
From: Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites
Comparative profiling of the Cayman Epigenetics library of drugs screened for inhibition activity against P. falciparum parasites. (A) Primary compound screening of 95 drugs that inhibit epigenetic modulators was performed using the SYBR Green I-based fluorescence assay for asexual parasites (strains 3D7, 96 h drug pressure on ring stage parasites) and the pLDH assay for early and late stage gametocytes (strain NF54, 72 h drug pressure each). The heatmap shows inhibition of asexual parasites and early (EG) and late stage (LG) gametocytes at 1 and 5 µM drug pressure. The color scale indicates the percentage inhibition of drug treatment normalized to 100% viable parasites. Compounds with similar inhibition profiles were hierarchically clustered based on Euclidean distance using R Software (v3.6.0. www.r-project.org/). (B) Distribution of compounds with >50% activity per life cycle stage based on their inhibitor classification within the Caymans library. (C) Epi-drug library composition based on inhibitor classification, targeting epigenetic modifiers, with the number of compounds per class indicated. Protein arginine methyltransferase (PRMT), DNA demethylase (DNDM), DNA methyltransferase (DNMT), histone demethylase (HDM), histone lysine methyltransferase (HKMT), lysine-specific demethylase (LSD), histone acetyltransferase (HAT), histone deacetylase (HDAC). Inhibition at 5 μM (%) was compared between asexual parasites (circle size; n = 3) and early (EG) & late (LG) stage gametocytes (n = 1); separated based on the inhibitor type (colour scale corresponding to inhibitor classification as in (B). Compounds with multi-stage activity is identified in the red block and those with asexual and EG preference in the blue block. SHA: suberohydroxamic acid; 3-DC: 3-deazaneplanocin.
