Separation of anti-angiogenic and cytotoxic activities of borrelidin by modification at the C17 side chain.
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.
Wilkinson
Barrie
B
Biotica Technology Ltd, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK. barrie.wilkinson@biotica.com
Gregory
Matthew A
MA
Moss
Steven J
SJ
Carletti
Isabelle
I
Sheridan
Rose M
RM
Kaja
Andrew
A
Ward
Michael
M
Olano
Carlos
C
Mendez
Carmen
C
Salas
José A
JA
Leadlay
Peter F
PF
vanGinckel
Rob
R
Zhang
Ming-Qiang
MQ
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
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003503:Cyclobutanes; D005233:Fatty Alcohols; C005066:borrelidin