Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead for Trypanosoma brucei Inhibitors.

ABSTRACT: Human African trypanosomiasis (HAT), or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and transmitted through the bite of infected tsetse flies. The disease is considered fatal if left untreated. To identify new chemotypes against Trypanosoma brucei, previously we identified 797 potent kinase-targeting inhibitors grouped into 59 clusters plus 53 singleton compounds with at least 100-fold selectivity over HepG2 cells. From this set of hits, a cluster of diaminopurine-derived compounds was identified. Herein, we report our medicinal chemistry investigation involving the exploration of structure-activity and structure-property relationships around one of the high-throughput screening (HTS) hits, N²-(thiophen-3-yl)-N⁶

SUBMITTER: Singh B 

PROVIDER: S-EPMC8372979 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature