Epigenetic Therapeutic Potential of Dulcitol, a Sugar Alcohol, as a Multi-Target HDAC Inhibitor against cervical cancer: Insights from In Silico Investigations
Kakali Sarkar1, Maria Debbarma1, Aishi Chakraborty1, Sudhan Debnath2, Samir Kumar Sil1∗
1Department of Human Physiology, Tripura University, Suryamaninagar, Tripura (West), 799022, India
2Department of Chemistry, Netaji Subhash Mahavidyalaya, Udaipur, Gomati, Tripura, 799114, India
Abstract: Recent studies have highlighted dulcitol (galactitol), a natural sugar alcohol, as a promising molecule with emerging anticancer potential. It has been shown that it promotes apoptosis, modulates oxidative stress and autophagic pathways, and inhibits proliferation, migration, and metastasis in multiple cancer types, such as glioma, hepatocellular, and triple-negative breast cancers. Histone deacetylase (HDAC) inhibitors are emerging as key “epigenetic weapons” against cancer. However, until now none of the studies have explored the role of dulcitol in epigenetic regulation through inhibition of HDACs. This study, therefore, was designed to evaluate the epigenetic regulatory role of dulcitol as a multi-target inhibitor of HDAC2, HDAC3, and HDAC8—key epigenetic modulators overexpressed in cervical cancer—through in silico analysis. Molecular docking showed that this multi-targeted inhibitor had stronger binding affinities than that of the FDA-approved inhibitors, interacting with key amino acids and the Zn2+ ion in active sites. ADMET analysis confirmed its favorable safety profile, with no significant hepatotoxicity, carcinogenicity, mutagenicity, immunogenicity or cytotoxicity. Additionally, molecular dynamics simulations demonstrated very stable HDAC-dulcitol interactions over 100 ns. This study provides strong in silico evidence for considering this sugar alcohol as a novel epigenetic therapeutic candidate for cervical cancer, though further experimental validation is warranted.
Key Words: Dulcitol; Multi-targeted inhibitor; Histone deacetylase; Cervical cancer