Exploration of Antiplasmodium Chemical Space Identifies New Inhibitors of β-Hematin Formation from Areas of Enrichment.

ABSTRACT: The Tres Cantos Antimalarial Set (TCAMS) library is a valuable resource for identifying hits for the antimalarial pipeline. We used principal component analysis (PCA) to explore this tranche of chemical space. Applying a set of 17 two-dimensional (2D) molecular descriptors, the chemical space was mapped in 2D PC space. Thereafter, the locations of known inhibitors and noninhibitors of synthetic hemozoin (β-hematin) formation, a well-established drug target during the asexual blood stage of the Plasmodium falciparum parasite life cycle, were superimposed onto the 2D map and counted. Within the +PC1, -PC2 quadrant, an area of enrichment emerged that could be used to predict the activity of test compounds. A subset of 861 TCAMS compounds (45 inhibitors and 816 noninhibitors) yielded a 27% hit

SUBMITTER: Thibaud JL 

PROVIDER: S-EPMC12908436 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature