Virtual screening of natural products as an inhibitor of DNA methyltransferase 1 enzyme for breast cancer disease

Breast cancer is the most prevalent cancer in woman worldwide. It has the highest number of new cases which amounted to 40 per 100,000 cases per year, 12.9% of which leads to death. Epigenetic alteration plays a vital role in the process of cancer cell formation and propagation. DNA methylation is one of the most common types of epigenetic alteration which generally leads to breast cancer. The DNA Methylation, a transfer of methyl group from S-adenosyl-methionine (SAM) to cytosine in the CpG dinucleotide, is catalysed by a DNA Methyltransferase-1 (DNMT1) enzyme. In the present study, we performed a virtual screening of natural product compounds as an inhibitor of the DNMT1 enzyme. Virtual screening was conducted on 26,731 natural products obtained from the NCBI PubChem database. Three steps of rigid and one step of flexible molecular docking simulations were performed using MOE 2014.09. Through the simulations, 10 best ligands based on the Gibbs free binding energies ΔG _binding ) and the ligand-enzyme complex interactions were identified. The pharmacological test was conducted to observe the physicochemical, toxicity, carcinogenicity-mutagenicity, and bioactivity properties by employing DataWarrior 4.7.2., Toxtree, Molinspiration, admetSAR, and SWISSADME software. The results revealed that three best ligands from the phenolic group were selected due to their exceptional pharmacological characteristics as the drug candidate for breast cancer therapy.