Using Theory To Reinterpret the Kinetics of Monofunctional Platinum Anticancer Drugs: Stacking Matters

• DOI: 10.1021/jacs.8b07875
• Publication Date: 2018-09-06T08:55:13Z
• Authors: Daniele Veclani; Andrea Melchior; Marilena Tolazzi; José P. Cerón-Car...
• Keywords: Nucleobase; Base (topology)

The monofunctional platinum drug phenanthriplatin (phenPt) blocks the replication of cancer cells even if it reacts with only one guanine base. However, there is still insufficient experimental data to improve its cytotoxicity and all previously proposed chemical modifications parent structure have resulted in a loss activity. We use theoretical tools illustrate key steps biological mechanisms phenPt; that is, activation water subsequent attack on DNA. Our simulations suggest measured kinetic parameters, which are based free nucleobases solution, need be reinterpreted because self-assembled stacked reactive adduct formed reaction inaccessible real constants reported here will help guide future work synthesis anticancer drugs.