Theoretical Study on the Mechanism of Alkylation At 0-6 Position of Guanine by Temozolomide and Bitc-Temozolomide

Temozolomide, an alkylating prodrug mainly used in the treatment of malignant glioblastoma(brain cancer). However, after giving dose of TMZ, there is a chance of reappearance of cancer cell after few days. The purpose of this study is to shade more light on mechanism of alkylation at O-6 position of guanine by TMZ and BITC-TMZ through computationally. This study will lead to gain of useful information of drug design and development. Along with the geometrical optimization using density functional theory, MEP and FMO parameters are also calculated. As the alkylation takes place at the O-6 of guanine of DNA. Therefore, this study mainly focus on the guanine sructures. The physiological properties of BITC-TMZ is found to be similar with the TMZ.