Anti-diabetic activity of bioactive compounds extract from Ixora brachiata leaf: In-vitro and molecular docking, dynamics simulation approaches

This study focused on Ixora brachiata, a plant belonging to the Rubiaceae family, with the aim of analyzing its bioactive compounds and their interactions with the PPARγ enzyme. Using a combination of molecular docking, virtual screening, ADME/Toxicity assessments, and molecular dynamics simulations, the research investigated 17 compounds isolated from I. brachiata. Among them, compound 11 (Sulfurous acid, decyl 2-propyl ester) and compound 15 (Di-N-decylsulfone) showed significant binding interactions with key residues (Ser317, His351, His477, and Tyr501) in the enzyme’s active site. The ADME/T properties of both compounds were found to meet acceptable standards, including characteristics such as human intestinal absorption, blood-brain barrier permeability, topological polar surface area, and percentage of absorption. Additionally, both compounds adhered to the Lipinski rule of five, indicating their potential for good bioavailability. The binding free energy for compound 15 was calculated to be -46.08 kcal/mol over 150 nanoseconds, primarily driven by favorable van der Waals interactions (-50.45 kcal/mol). Decomposition analysis revealed that residues Ser317, Val367, Met392 and Tyr501 played essential roles in the ligand binding process. The study findings were consistent with the known bioactivity of I. brachiata and underscored the significant role of van der Waals forces in the molecular binding process. Molecular dynamics simulations, along with toxicity assessments, provided further insights into the safety and potential of these natural compounds for biomedical applications. Notably, compound 15 demonstrated strong potential as a promising candidate for further development in therapeutic applications.