title: Separation of anti-angiogenic and cytotoxic activities of borrelidin by modification at the C17 side chain.
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.
authors.affiliation: Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK. barrie.wilkinson@biotica.com
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gregory
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Moss
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carletti
authors.forename: Rose M
authors.initials: RM
authors.lastname: Sheridan
authors.forename: Andrew
authors.initials: A
authors.lastname: Kaja
authors.forename: Michael
authors.initials: M
authors.lastname: Ward
authors.forename: Carlos
authors.initials: C
authors.lastname: Olano
authors.forename: Carmen
authors.initials: C
authors.lastname: Mendez
authors.forename: José A
authors.initials: JA
authors.lastname: Salas
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
authors.forename: Rob
authors.initials: R
authors.lastname: vanGinckel
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zhang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D003503:Cyclobutanes / Q000737:chemistry*; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003503:Cyclobutanes; D005233:Fatty Alcohols; C005066:borrelidin