Total synthesis and anti-tubulin activity of epi-c3 analogues of cryptophycin-24.
Epi-C3-cryptophycin-24, epi-C3-m-chlorobenzyl-cryptophycin-24, and the corresponding styrenes were synthesized and tested in vitro against the MCF-7 and multidrug-resistant MCF-7/ADR breast cancer cell lines and in an in vitro tubulin assembly assay. The results demonstrate that the S configuration at the C3 stereocenter is not required to induce potent cytotoxicity and the m-Cl substituent present on the C10 side chain did not induce any large change in activity.
Buck
Suzanne B
SB
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Drive, Lawrence, KS 66045-7582, USA.
Huff
Jacquelyn K
JK
Himes
Richard H
RH
Georg
Gunda I
GI
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers; D045744:Cell Line, Tumor; D047630:Depsipeptides; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry*
D000970:Antineoplastic Agents; D001704:Biopolymers; D047630:Depsipeptides; D010456:Peptides, Cyclic; D013343:Styrenes; D014404:Tubulin; C096566:arenastatin A