In Silico Studies on Fingolimod and Cladribine Binding to p53 Gene and Its Implication in Prediction of Their Carcinogenicity Potential

New drugs namely; cladribine and fingolimodare known to be effective in treatment of multiple sclerosis (MS). The interaction of these drugs with the promoter region of the p53 gene may alter p53role in cancer progression. The aim of this study was to known the interaction of these compounds with p53 gene.
Binding free energy of the cladribine, fingolimod and their modified drugs for the p53 gene promoter were investigated using docking, 100 ns molecular dynamics simulations and MM/PBSA calculation.
The results showed that both cladribine and modified cladribine (replacing -OH on carbon 3´ ribose sugar with -CH3 group) can bind the minor groove of p53 promoter, and inhibit the binding of transcription factors and expression of p53. However, fingolimodand its derivatives showed relatively weaker interaction with p53 promoter
Based on in silico studies we showed that the binding of cladribine to the p53 gene is stronger than that of fingolimod, hence it seems that the former drug can pose potential carcinogenic effects. The binding power and carcinogenic effect of sm-fingolimod (removing four carbons from its aliphatic tail) is more than that of fm-fingolimod (removing one carbon from its aliphatic tail).