Unsymmetric hydroxylamine and hydrazine BAM15 derivatives as potent mitochondrial uncouplers.

ABSTRACT: Chemical mitochondrial uncouplers are protonophoric, lipophilic small molecules that transport protons from the mitochondrial intermembrane space into the matrix independent of ATP synthase, thus uncoupling nutrient oxidation from ATP production. Our previous work identified BAM15 (IC₅₀ 0.27 μM) as a potent and efficacious mitochondrial uncoupler with potential for obesity treatment. In this paper, we investigate in vitro and in vivo properties of hydroxylamine and hydrazine BAM15 derivatives and reveal the high uncoupling nature of these compounds. Our structure-activity relationship studies revealed that the hydroxylamine BAM15 analogs are more potent than hydrazine ones. For example, the most potent of the hydrazine series was 5a with an EC₅₀ value of 4.6 μM and 10

SUBMITTER: Quinlan JE 

PROVIDER: S-EPMC11752867 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature