COMPUTATIONAL EXPLORATION OF PSIDII GUAJAVAE FOLIUM BIOACTIVE COMPOUNDS AS NOVEL DPP-IV INHIBITORS FOR TYPE 2 DIABETES MELLITUS INTERVENTION

Folasade O. Ajao, Adeola F. Ehigie, Tope T. Odunitan, Opeyemi E. Atanda, Paul B. Ayoola and Lamidi W. B. Olaniyan*

ABSTRACT

Type 2 diabetes mellitus (T2DM) presents a significant global health challenge, necessitating the exploration of novel therapeutic interventions. In this computational study, we investigated Psidii Guajavae Folium (PGF) bioactive compounds as potential inhibitors of Dipeptidyl Peptidase IV (DPP-IV), a key enzyme implicated in T2DM pathophysiology. A total of 60 bioactive compounds, including the reference drug Teneligliptin, were subjected to molecular docking against the DPP-IV protein target. Thirteen compounds exhibiting pronounced binding affinities (-7.73 Kcal/mol to -6.6 Kcal/mol) compared to Teneligliptin (-6.5Kcal/mol) were further evaluated for drug-likeness and ADMET properties. Among these, four phytochemicals (Emetine, Linoelaidic Acid, Doconexent, and Clionasterol) demonstrated commendable drug-like characteristics and specificity, adhering to Lipinski's rule of five. Molecular dynamics simulations provided insights into the stability and dynamic behavior of the ligand-protein complexes, with Emetine emerging as the most promising inhibitor, followed closely by Linoelaidic Acid. MMGBSA calculations highlighted Emetine's robust total binding energy (-41.6889Kcal/mol) and favorable interaction profile, suggesting its potential as an effective DPP-IV inhibitor for T2DM intervention. Our findings underscore the promise of PGF-derived compounds as novel therapeutics for managing T2DM and warrant further experimental validation.

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