Phytochemicals as DNMTs inhibitors for targeted therapy in head and neck cancer: An in-silico study

Head and neck cancer (HNC) remains a challenge in oncology due to its aggressive metastatic behavior, complex treatment requirements, and increasing global incidence. Increasing morbidity and mortality rates require innovative treatment strategies to enhance patient outcomes. DNA methylation is regulated by enzymes, such as DNA methyltransferases (DNMTs), which play a crucial role in altering gene expression in HNC. This study utilized a computational approach to identify phytochemicals as putative DNMT inhibitors for HNC. We employed AutoDock-based virtual screening to identify phytochemicals that exhibit a strong binding affinity for the enzymes DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L. Pharmacokinetic and toxicity properties were evaluated using ADMET screening. MM-PBSA analysis showed the stability and binding strengths of the interactions between the selected phytochemicals and the DNMTs. The results indicated that theaflavin exhibited the lowest binding energy with DNMT1 (−9.5 kcal/mol) and DNMT3B (−9.7 kcal/mol), whereas EGCG showed −9.1 kcal/mol for DNMT2. Silibinin showed the lowest binding energy of −9.2 kcal/mol with DNMT3A, and delphinidin exhibited −8.3 kcal/mol with DNMT3L. These computational findings identify phytochemicals with potential to inhibit DNMTs, offering promising avenues for the treatment of HNC. This information lays the groundwork for future experimental and clinical investigations, drug development, and targeting epigenetic regulators such as DNMTs.