In-silico investigations into natural products as non-nucleoside DNA methyltransferase 1 inhibitors for treating epi-mutation in gastric cancer

Purpose: To explore in silico methods to search for the best reported non-nucleoside DNA methyltransferase 1 (DNMT1) inhibitor of epimutation in gastric cancer.
Methods: A dataset of reported non-nucleoside DNMT1 inhibitors was used to target the active site of crystallized DNMT1 protein. Molecular docking simulations were carried out using AutoDock 4.2.6 l. The results were analyzed using Discovery studio visualizer.
Results: In silico analysis of known natural non-nucleoside DNMT1 inhibitors gave genistein as the top ranked compound with ΔG of -6.39 Kcal/mol. Further, the results indicated that epigallocatechin gallate and curcumin are poor non-nucleoside DNMT1 inhibitors, as the in silico data suggest that they failed to bind to the catalytic site of DNMT1.
Conclusion: The results indicate that genistein is the top rated compound for DNMT1 inhibition. Previous in vitro and in vivo work by other researchers seem to validate the findings of the study.

Keywords
Epi-mutation; DNA methyltransferase; Non-nucleoside; DNMT1 inhibitor; Docking