Trypanocidal action of bisphosphonium salts through a mitochondrial target in bloodstream form Trypanosoma brucei.

ABSTRACT: Lipophilic bisphosphonium salts are among the most promising antiprotozoal leads currently under investigation. As part of their preclinical evaluation we here report on their mode of action against African trypanosomes, the etiological agents of sleeping sickness. The bisphosphonium compounds CD38 and AHI-9 exhibited rapid inhibition of Trypanosoma brucei growth, apparently the result of cell cycle arrest that blocked the replication of mitochondrial DNA, contained in the kinetoplast, thereby preventing the initiation of S-phase. Incubation with either compound led to a rapid reduction in mitochondrial membrane potential, and ATP levels decreased by approximately 50% within 1 h. Between 4 and 8 h, cellular calcium levels increased, consistent with release from the depolarized mitochondria

SUBMITTER: Alkhaldi AAM 

PROVIDER: S-EPMC4805778 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature