Theoretical Investigations and Density Functional Theory Based Quantitative Structure鈥揂ctivity Relationships Model for Novel Cytotoxic Platinum(IV) Complexes

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• 作者：Hristo P. Varbanov ; Michael A. Jakupec ; Alexander Roller ; Frank Jensen ; Markus Galanski ; Bernhard K. Keppler
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：January 10, 2013
• 年：2013
• 卷：56
• 期：1
• 页码：330-344
• 全文大小：850K
• 年卷期：v.56,no.1(January 10, 2013)
• ISSN：1520-4804

文摘

Octahedral platinum(IV) complexes are promising candidates in the fight against cancer. In order to rationalize the further development of this class of compounds, detailed studies on their mechanisms of action, toxicity, and resistance must be provided and structure鈥揳ctivity relationships must be drawn. Herein, we report on theoretical and QSAR investigations of a series of 53 novel bis-, tris-, and tetrakis(carboxylato)platinum(IV) complexes, synthesized and tested for cytotoxicity in our laboratories. The hybrid DFT functional wb97x was used for optimization of the structure geometry and calculation of the descriptors. Reliable and robust QSAR models with good explanatory and predictive properties were obtained for both the cisplatin sensitive cell line CH1 and the intrinsically cisplatin resistant cell line SW480, with a set of four descriptors.