In silico exploration natural compounds for the discovery of novel DNMT3A inhibitors as potential therapeutic agents for acute myeloid leukemia

In the current research, we focused on the critical role of DNA methylation in acute myeloid leukemia (AML) and the potential of DNMT3A inhibitors as therapeutic agents. The aberrant activity of DNMT3A is linked to poor patient outcomes, prompting the need for effective inhibitors. The primary objective was to identify and evaluate natural compounds that could serve as novel DNMT3A inhibitors, thereby offering new avenues for AML treatment. We employed a comprehensive computational approach, utilizing molecular docking, pharmacophore modelling, and molecular dynamics simulations. We screened a diverse library of natural compounds, assessing their binding affinities and interactions with the DNMT3A protein. Through the analysis, we identified two promising compounds, CNP0375130 and CNP0256178, which exhibited strong binding affinities and stable interactions with DNMT3A. The molecular dynamics simulations revealed that these compounds maintained structural stability throughout the simulation period, indicating their potential as effective inhibitors. The findings suggest that CNP0375130 and CNP0256178 are viable candidates for further development as DNMT3A inhibitors in AML therapy. This research not only enhances our understanding of DNMT3A's role in AML but also paves the way for future studies aimed at translating these findings into clinical applications. The schematic representation of the complete screening steps used in this study