Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites.

ABSTRACT: The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit β-hematin (synthetic hemozoin) formation by high throughput screening. Here, a library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated, and Bayesian statistics used to predict β-hematin and Plasmodium falciparum growth inhibition. Filtering predicted inactives and compounds with negligible aqueous solubility reduced the library to 35,124. Further narrowing to compounds with terminal aryl ring substituents only, reduced the library to 18, 83% of which were found to inhibit β-hematin formation <100 μM and 50% parasite growth <2 μM. Four compounds showed nanomolar parasite growth inhibition activities, no cross-resistance in a chloroquine resistant strain and low cytotoxicity. QSAR analysis show

SUBMITTER: L'abbate FP 

PROVIDER: S-EPMC6232849 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature