Borges Rosivaldo S, Carneiro Agnaldo S, Barros Tainá G, Barros Carlos A L, Neto Antonio M J Chaves, da Silva Albérico B F
Núcleo de Estudos e Seleção de Moléculas Bioativas, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-110, Belém, PA, Brazil,
J Mol Model. 2014 Dec;20(12):2541. doi: 10.1007/s00894-014-2541-9. Epub 2014 Dec 11.
Quinones represent an important class of biological compounds, but are also involved with toxicological intermediates and among their hazardous effects include cytotoxicity, immunotoxicity, and carcinogenesis. The structure-toxicity relationship for quinone derivatives has been used to cytotoxicity or cytoprotective effects by redox mechanism is determined using quantum chemical calculations through the density functional theory (DFT). According to our DFT study, the electron acceptance is related with LUMO, electron affinity, and stabilization energy values. The highest spin density distribution in the heteroatoms is more favored for the more cytotoxic compounds. The electrophilic capacities of these compounds have been related with LUMO values. The cytotoxic properties of quinones are related to the stabilization energy after electron accepting by redox mechanism. Electron affinity is the most relevant parameter related to toxicity mechanism. Regioisomers has different electrophilic capacity. The electrophilicity increases on molecules containing electron-withdrawing groups (EWG) and reduces on molecules containing electron-donating groups (EDG). These results explain the toxic difference between natural and synthetic quinone derivatives and can be used in the design and study of new drugs.
醌类是一类重要的生物化合物,但也与毒理学中间体有关,其有害影响包括细胞毒性、免疫毒性和致癌作用。醌类衍生物的结构-毒性关系已被用于通过氧化还原机制确定细胞毒性或细胞保护作用,这是通过密度泛函理论(DFT)进行量子化学计算来实现的。根据我们的DFT研究,电子接受与最低未占分子轨道(LUMO)、电子亲和能和稳定能值有关。对于细胞毒性更强的化合物,杂原子中最高的自旋密度分布更受青睐。这些化合物的亲电能力与LUMO值有关。醌类的细胞毒性特性与通过氧化还原机制接受电子后的稳定能有关。电子亲和能是与毒性机制最相关的参数。区域异构体具有不同的亲电能力。含有吸电子基团(EWG)的分子亲电性增加,而含有供电子基团(EDG)的分子亲电性降低。这些结果解释了天然和合成醌类衍生物之间的毒性差异,并可用于新药的设计和研究。