Bridging Converts a Noncytotoxicnor-Paclitaxel Derivative to a Cytotoxic Analogue by Constraining It to the T-Taxol Conformation
作者： Shoubin Tang , Chao Yang , Peggy Brodie , Susan Bane , Rudravajhala Ravindra
DOI: 10.1021/OL061438S
关键词: Derivative (chemistry) 、 Cytotoxic T cell 、 Stereochemistry 、 Tubulin 、 Chemistry 、 Paclitaxel 、 Plasma protein binding 、 Molecule 、 Physical and Theoretical Chemistry 、 Organic chemistry 、 Biochemistry
摘要: The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test T-Taxol conformational hypothesis. Although unbridged 3 is essentially noncytotoxic, analogue strongly cytotoxic. This result provides strong evidence for conformation as bioactive tubulin-binding paclitaxel.
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