Structure–Cytotoxicity Relationships of Analogues of N14-Desacetoxytubulysin H

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• 作者：Dorin Toader ; Fengjiang Wang ; Lakshmaiah Gingipalli ; Melissa Vasbinder ; Mark Roth ; Shenlan Mao ; Michael Block ; Jay Harper ; Sambaiah Thota ; Mei Su ; Jianquo Ma ; Vahe Bedian ; Adeela Kamal
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：December 8, 2016
• 年：2016
• 卷：59
• 期：23
• 页码：10781-10787
• 全文大小：344K
• ISSN：1520-4804

文摘

Herein we report structure–cytotoxicity relationships for analogues of N¹⁴-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of cancer.