Fluorescent probes of the apoptolidins and their utility in cellular localization studies.

ABSTRACT: Apoptolidin?A has been described among the top 0.1% most-cell-selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin?A consists of a 20-membered macrolide with mono- and disaccharide moieties. In contrast to apoptolidin?A, the aglycone (apoptolidinone) shows no cytotoxicity (>10??M) when evaluated against several tumor cell lines. Apoptolidin?H, the C27 deglycosylated analogue of apoptolidin?A, displayed sub-micromolar activity against H292 lung carcinoma cells. Selective esterification of apoptolidins?A and H with 5-azidopentanoic acid afforded azido-functionalized derivatives of potency equal to that of the parent macrolide. They also underwent strain-promoted alkyne-azido cycloaddition reactions to provide access to fluorescent and biotin-functionalized probes. Microscopy studies demonstrate apoptolidins?A and H localize in the mitochondria of H292 human lung carcinoma cells.

SUBMITTER: DeGuire SM 

PROVIDER: S-EPMC4293314 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature