Identification of Potential Phytochemical Inhibitors of DNMT1 through Virtual Screening and Molecular Dynamics Simulation to Promote DiabeticWound Healing

Introduction: DNA methyltransferase 1 (DNMT1) has recently emerged as a potential therapeutic target for diabetic wound healing (DWH). Studies have shown that inhibition of DNMT1 may be valuable in accelerating DWH. Method: Virtual screening of 3,646 phytochemicals derived from the IMPPAT database was performed against DNMT1. This was followed by exhaustive docking, ADMET analysis, and molecular dynamics simulation to identify potential phytochemical inhibitors of DNMT1. Results: Out of the 17967 phytochemicals present in the database, 3646 of them were chosen for fast screening based on their drug-likeness properties. When compared with the reference compound, over 2500 compounds exhibited lower binding energies. The top 972 compounds having binding energies ≤ 8.7 kcal/mol were chosen, and 40 out of 972 compounds passed through the ADMET filters. These were then subjected to molecular docking, and the compound with the least binding energy and favourable hydrogen bonding was then selected for molecular dynamics simulation. The stability of the Oroxindin-DNMT1 complex was further validated by molecular dynamics simulation studies. Discussion: Derived from the traditional Chinese remedy Huang-Qin, Oroxindin has been shown to possess a range of pharmacological effects, including anti-inflammatory, antitumor, and antioxidant properties. The wound-healing potential of Oroxindin has to be evaluated in vitro and in vivo for further validation. Conclusion: Oroxindin emerged as the ideal phytochemical among the 3,646 screened. The ability of Oroxindin to accelerate DWH still needs to be evaluated in vitro and in vivo for further validation.