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

  • Bioorg Med Chem Lett. 2006 Nov 15;16(22):5814-7. doi: 10.1016/j.bmcl.2006.08.073.
Barrie Wilkinson  1 ,  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
Affiliations
  • 1. Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK. [email protected]
PMID: 16962775 DOI: 10.1016/j.bmcl.2006.08.073
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.