Identification of potent inhibitors of DNA methyltransferase 1 (DNMT1) through a pharmacophore-based virtual screening approach.

摘要: DNA methylation is an epigenetic change that results in the addition of a methyl group at carbon-5 position cytosine residues. methyltransferase (DNMT) inhibitors can suppress tumour growth and have significant therapeutic value. However, established are limited their application due to substantial cytotoxicity. Additionally, standard drugs for DNMT inhibition non-selective analogues with considerable cytotoxic side-effects. In present study, we designed workflow by integrating various ligand-based structure-based approaches discover new agents active against DNMT1. We derived pharmacophore model help available DNMT1 inhibitors. Utilising this model, performed virtual screening Maybridge chemical library identified hits were then subsequently filtered based on Naive Bayesian classification model. The molecules returned from subjected ensemble docking. selected 10 biological assay inspecting interactions portrayed these molecules. Three out ten tested compounds shown inhibitory activity. These also found demonstrate potential cellular proliferation human breast cancer MDA-MB-231 cells. utilized multi-step protocol identify DNMT1, which offers starting point develop more potent as anti-cancer agents.