Synthesis, modeling, and anti-tubulin activity of a D-seco paclitaxel analogue |
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Authors: | Barboni Luciano Giarlo Guido Ricciutelli Massimo Ballini Roberto Georg Gunda I VanderVelde David G Himes Richard H Wang Minmin Lakdawala Ami Snyder James P |
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Institution: | Dipartimento di Scienze Chimiche, Università di Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy. georg@ku.edu |
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Abstract: | reaction: see text] We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel. |
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