Mechanism Study of the Reduction of O6-4-Nitrobenzyl-Guanine Catalysed by FMNH

作者: 肖家斌 , 孙国辉 :北京工业大学生命科学与生物工程学院,北京;

关键词: AGT抑制剂前体药物硝基还原酶质子电子耦合转移AGT Inhibitor Prodrug Nitroreductase Proton Coupled Electron Transfer


Abstract: The reduction mechanism of O6-Alkylguanine DNA Alkyltransferase inhibitor of the nitro group of the pro-drug in the Nitro Reductase (NTR) was studied by using the Density Functional Theory (DFT). The results showed that the transitions of TS2 (yielding nitroso compound) and TS5 (yielding aniline compound) were the rate-limiting steps among the six reaction transition states. Single water molecule-mediated proton coupled electron transfer can lower the reactive activation energy of TS2 and TS6; thus it is speculated that water-mediated proton coupled electron transfer is the optimal reaction pathway of TS2 and TS6. The reduction mechanism of the prodrug of nitro aromatic compound and the involved reaction thermodynamics can be clearly presented by the potential energy curve. This study can provide a theoretical basis for designing more efficient hypoxia-activated AGT inhibitors with less side effects.

文章引用: 肖家斌 , 孙国辉 (2016) FMNH催化O6-4-硝基苄基鸟嘌呤还原机理的研究。 药物资讯, 5, 25-32. doi: 10.12677/PI.2016.52005


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