Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel

L Sun, JM Veith, P Pera, RJ Bernacki, I Ojima

Index: Sun, Liang; Veith, Jean M.; Pera, Paula; Bernacki, Ralph J.; Ojima, Iwao Bioorganic and Medicinal Chemistry, 2010 , vol. 18, # 19 p. 7101 - 7112

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Citation Number: 15

Abstract

Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol ...