In:
Chemistry – A European Journal, Wiley, Vol. 15, No. 23 ( 2009-06-02), p. 5799-5813
Abstract:
A drug of two halves : New artificial compounds composed of a macrosphelide core skeleton and an epothilone side chain were designed and synthesized. These compounds were more potent inducers of apoptosis than the parent natural‐type macrosphelides. magnified image Various artificial macrosphelides were designed and synthesized, including ring‐enlarged analogues and epothilone‐hybrid compounds. Syntheses were accomplished in an efficient manner by using a ring‐closing metathesis (RCM) strategy in a key macrocyclization step. Biological evaluation of these new macrosphelide‐based derivatives revealed that several epothilone hybrids, in which a thiazole‐containing side chain was incorporated, exhibited potent apoptosis‐inducing activity toward human lymphoma cells. These activities were considerably enhanced relative to those of natural macrosphelide compounds. Structure–activity relationship studies revealed that the “ene‐dicarbonyl” substructure is apparently essential for bioactivity.
Type of Medium:
Online Resource
ISSN:
0947-6539
,
1521-3765
DOI:
10.1002/chem.200802661
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
1478547-X
Permalink