Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport.

ABSTRACT: Leelamine is an anticancer chemotherapeutic agent inhibiting intracellular cholesterol transport. Cell death mediated by leelamine occurs due to the lysosomotropic property of the compound, its accumulation in the lysosome, and inhibition of cholesterol transport leading to lack of availability for key processes required for functioning of cancer cells. The present study dissects the structure-activity-relationship of leelamine using synthesized derivatives of leelamine and abietic acid, a structurally similar compound, to identify the moiety responsible for anti-cancer activity. Similar to leelamine, all active derivatives had an amino group or a similar moiety that confers a lysosomotropic property to the compound enabling its accumulation in the lysosome. Active derivatives inhibited in

SUBMITTER: Gowda R 

PROVIDER: S-EPMC5438648 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature