MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC POTENTIAL OF CERTAIN PLANTS

ABSTRACT

Glaucoma is a neurodegenerative condition that harms the primary nerve connecting to the eye, known as the optic nerve, situated at the rear of the eye. Using natural precursor compounds identified via computational screening and prediction of pharmacokinetics, the development of potent precursor molecules for the treatment of glaucoma becomes viable. This study aims to perform a computational analysis of the phytoconstituents found in some medicinal plants historically employed in the management of glaucoma. Ligand preparation involved obtaining SDF format files from the PubChem database and using the ligprep panel in Maestro 12.8. Protein preparation included downloading protein structures from RCSB directory and utilizing the protein preparation wizard, followed by receptor grid generation to define active sites for docking. Molecular docking was performed using Maestro, and pharmacokinetic parameter predictions were conducted using SwissADME online server to assess pharmacokinetic and toxicity properties of test compounds. Results from the study revealed that 7 phytoconstituents from Crocus sativus had higher binding affinity than the standard molecule latanoprost against the PGF2α receptor protein, up to 50 exhibited higher binding affinity than butanamide against the CA receptor while 3 compounds were seen to have higher affinity than bumetanide against the α-2 adrenoceptor. 11 phytoconstituents from Ginkgo biloba were observed to have higher binding affinity than the standard against α-2 adrenoceptor, 94 compounds had higher binding affinity than butanamide against the CA target while 36 compounds had higher score than PGF2α standard. 7 phytoconstituents from Scutellaria baicalensis had higher binding affinity than the standard molecule brimonidine, 59 compounds had higher binding affinity than butanamide while 41 compounds had higher docking affinities than the standard against PGF2α and all were selected for further screening. ADMET analysis revealed favorable pharmacokinetic and toxicity properties while post docking analysis showed the molecular interactions of ligands with the receptors.