Deregulationin the addition of methyl group on the cytosine C-5 position is widely associated with various diseases such as cancer. There are currently two nucleoside drugs approved by the FDA for the treatment of certain types of cancer (5-aza and 5-aza-2deoxicitidina). However, they have very low selectivity and high toxicity. This makes imperative to search new non-nucleoside inhibitors with lesser adverse effects.<br/>This study presents a systematic analysis of a comprehensive database of inhibitors of DNA methyltransferase 1 (DNMT1) constructed using information in public molecular databases and scientific literature searching. The molecules were studied using chemical properties and chemical diversity using complementary similarity metrics and scaffolds diversity. Through these analyses, we identify the best molecular scaffolds with the highest enrichment factor. Such scaffolds represent potentially privileged structures of selective inhibitors against DNMT1. Thesescaffolds were used to develop a3D pharmacophore model. This model was used as query in a virtual screening for the identification of new non-nucleoside scaffolds with activity against DNMT1.

Pharmacophore modeling of non-nucleoside DNA methyltransferase inhibitors based on a chemoinformatic analysis

251st National Meeting (2016)

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