Microchemical analysis, molecular docking, and pharmacokinetic profiling of bioactive compounds from traditional Konyak Polyherbal formulations targeting VEGFR2 protein

Abstract

Medicinal plants are good source of numerous bioactive compounds with noteworthy pharmacological properties. This study solely focused on a polyherbal formulation traditionally used by the Konyak tribe of Nagaland. Comprising of Persicaria maculosa, Acorus calamus, Erythrina variegata, Strereospermum chelonoides, and Oroxylum indicum prepared in a ratio of 1:1:3:1:3. GC–MS analysis identified sterols, triterpenoids, and fatty acids, which underwent comprehensive molecular docking against VEGFR2 (PDB ID: 4AG8) using Autodock Vinna. 9, 19-Cyclolanost-24-en-3-ol (−9.1 Kcal/mol) and Pregnan-20-one (−8.4 Kcal/mol), exhibited affinities comparable to Axitinib (−9.8 Kcal/mol), with selectivity over FGFR1 (PDB ID: 4F63). 100 ns GROMACS molecular dynamic simulation confirmed all ligand achieved RMSD equilibration (<0.25 nm post initial phase), with Cholestan-3-ol showing lowest fluctuations. Hydrogen bond analysis revealed persistent hinge interactions (Glu885, Cys919;>60% occupancy), with Pregnan-20-one maintaining 4–6 bonds. RMSD‑hydrogen bond correlation demonstrated thermodynamic favorability, as ligands 9,19-Cyclolanost-24-en-3-ol, Pregnan-20-one, Cholestan-3-ol greater conformational stability. ADMET profiling indicated low acute toxicity (Class 4–6) and acceptable physiochemical properties despite sterol lipophilicity. These integrated computational results preliminarily validate the formulation triterpenoid/sterol components as a promising VEGFR2 selective anti angiogenic agents, warranting experimental validation for colon cancer therapeutic.