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The cryptophycins: Their synthesis and anticancer activity
Author(s) -
Eggen MariJean,
Georg Gunda I.
Publication year - 2002
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.10002
Subject(s) - antimitotic agent , tubulin , microtubule , stereochemistry , chemistry , convergent synthesis , in vivo , nostoc , amide , structure–activity relationship , depsipeptide , biochemistry , biology , cyanobacteria , computational biology , in vitro , microbiology and biotechnology , genetics , bacteria
The cryptophycins are a unique family of 16‐membered macrolide antimitotic agents isolated from the cyanobacteria Nostoc sp. Their molecular target is tubulin protein wherein they are the most potent known stabilizers of microtubule dynamics and depolymerize microtubules at higher concentrations. They also deactivate the Bcl2 protein and produce apoptotic response much more quickly and at considerably lower concentrations than clinically utilized compounds. The presence of several amide and ester linkages within the cryptophycin core provides access to very convergent total synthetic approaches. Likewise, the modularity of the structure renders their synthesis amenable to structure‐activity studies in several regions of the molecule. The in vivo hydrolytic instability of the C5 ester was a key obstacle to the successful identification of a clinical candidate. This problem was ameliorated by increased substitution at C6 as in the presence of gem‐dimethyl substitution in the clinical candidate, cryptophycin‐52. © 2002 John Wiley & Sons, Inc. Med Res Rev, 22, No. 2, 85–101, 2002; DOI 10.1002/med.10002