A Molecular Modelling Analysis of Luliconazole, Lanconazole and Bifonazole
In this study, molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations have been carried out to obtain insight into their toxicity. The results of the analyses show that LLZ, LCZ and BFZ have LUMO-HOMO energy differences ranging from 4.5 to 4.9 eV, indicating that the compounds would be moderately inert with BFZ being the most inert one. The molecular surfaces of all the compounds are found to possess significant amounts of positively charged electron-deficient regions so that they may be subject to nucleophilic attacks by glutathione and nucleobases in DNA, thus causing cellular toxicity due to glutathione depletion and DNA damage due to oxidation of nucleobases. However, because of kinetic inertness of the molecules, the rates of such adverse reactions are expected to be low.
Cited References Fulltext