Halohydrin analogues of cryptophycin 1: synthesis and biological activity.
The chloro-, bromo-, and iodo-derivatives 2-4 of the antimitotic drug cryptophycin 1 were synthesized by opening the epoxide ring. The biological activities of the compounds were tested in an in vitro microtubule assembly and a cell proliferation assay. The chloro-derivative 2 showed lower activity in the tubulin assay compared to 3 and 4, but they all showed similar inhibition in the proliferation assay.
Georg
G I
GI
Department of Medicinal Chemistry, University of Kansas, Lawrence 66045, USA.
Ali
S M
SM
Stella
V J
VJ
Waugh
W N
WN
Himes
R H
RH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047630:Depsipeptides; D006207:Half-Life; D007189:Indans / Q000737:chemistry; D008546:Melanoma, Experimental / Q000473:pathology; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047630:Depsipeptides; D007189:Indans; D010456:Peptides, Cyclic; D014404:Tubulin; C088419:cryptophycin