Synthesis and biological evaluation of (-)-laulimalide analogues.
[reaction: see text] The syntheses of five laulimalide analogues are described, incorporating modifications at the C(16)-C(17)-epoxide, the C(20)-alcohol, as well as the C(1)-C(3)-enoate of the parent natural product. The resultant analogues are active in drug-sensitive HeLa and MDA-MB-435 cell lines. Significantly, like laulimalide, these analogues are poor substrates for the drug transport protein P-glycoprotein (Pgp) and are thus effective against Taxol-resistant cell lines.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California 94305, USA. wenderp@stanford.edu
Hegde
Sayee G
SG
Hubbard
Robert D
RD
Zhang
Lei
L
Mooberry
Susan L
SL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000737:chemistry; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D018942:Macrolides; D015394:Molecular Structure; D013237:Stereoisomerism; D043823:Taxoids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D018942:Macrolides; D043823:Taxoids; C117305:laulimalide