Bioorganic & Medicinal Chemistry Letters 2006-11-15

Separation of anti-angiogenic and cytotoxic activities of borrelidin by modification at the C17 side chain.

Barrie Wilkinson, Matthew A Gregory, Steven J Moss, Isabelle Carletti, Rose M Sheridan, Andrew Kaja, Michael Ward, Carlos Olano, Carmen Mendez, José A Salas, Peter F Leadlay, Rob vanGinckel, Ming-Qiang Zhang

Index: Bioorg. Med. Chem. Lett. 16 , 5814-7, (2006)

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Abstract

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.