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Synthesis and Biological Evaluation of 12,13‐Cyclopropyl and 12,13‐Cyclobutyl Epothilones
Author(s) -
Nicolaou K. C.,
Namoto Kenji,
Li Jim,
Ritzén Andreas,
Ulven Trond,
Shoji Mitsuru,
Zaharevitz Dan,
Gussio Rick,
Sackett Dan L.,
Ward Rita D.,
Hensler Anne,
Fojo Tito,
Giannakakou Paraskevi
Publication year - 2001
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20010105)2:1<69::aid-cbic69>3.0.co;2-8
Subject(s) - epothilones , epothilone , chemistry , stereochemistry , molecule , magenta , combinatorial chemistry , organic chemistry , materials science , inkwell , composite material
An unambiguous chemical synthesis and biological evaluation of the title compounds revealed their comparable potencies to natural epothilone A ( 1 ) against tumor cell lines, shedding further light on structure–activity relationships within the epothilone class. The picture shows a superposition of molecular models of 1 and 12,13‐cyclopropyl epothilone A ( 2 ) (C atoms in magenta and white, respectively) in the tubulin binding site. A water molecule hydrogen‐bonded to 1 (H atoms in magenta) is displaced upon binding of 2 (H atoms in white) which makes hydrophobic interactions with the side chain of Leu 273.