-
Separation of anti-angiogenic and cytotoxic activities of borrelidin by modification at the C17 side chain.
Wilkinson B,
Gregory MA,
Moss SJ,
Carletti I,
Sheridan RM,
Kaja A,
Ward M,
Olano C,
Mendez C,
Salas JA,
Leadlay PF,
vanGinckel R,
Zhang MQ.
Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK. barrie.wilkinson@biotica.com
A set of novel borrelidin analogues have been prepared by precursor-directed biosynthesis. Structure-activity relationship analysis suggests that steric structural arrangement within the C17 side chain is important for differentiating cytotoxic and anti-angiogenic activities. A C17-cyclobutyl analogue 3 was found to have markedly increased selectivity for in vitro angiogenesis inhibition over cytotoxicity and is therefore potentially useful as an anticancer agent.
PMID: 16962775 [PubMed - indexed for MEDLINE]
-