Neuroprotective potentials of Ageratum conyzoides phytoconstituents via inhibition of monoamine oxidase: An in-silico study

Abstract

A surge of monoamine oxidase (MAO) causes neurodegenerative disorders like depression linked to suicides among youths. The goal of this work was to use a molecular docking technique to predict the neuroprotective potentials of phytoconstituents found in Ageratum conyzoides leaves (ACL), a popular folk remedy for neurological disorders. The 23 phytoconstituents previously found in ethanol leaf extract of ACL (ACL1-23) were identified and their 3D structures were either sketched (ACD/ChemSketch) or downloaded from the PubChem website. MAO was the target protein, and phenelzine (PNZ) was the standard inhibitor. The protein structure was obtained from the Protein Data Bank and processed for docking with UCSF Chimera. Before molecular docking with the AutoDock Vina Plugin PyRx, the 23 ACL bioactive compounds were tested for blood-brain barrier (BBB) permeability and other pharmacological characteristics. The protein-ligand interactions were visualized using the Discovery Studio 2020 after docking. The result revealed that all other ACL bioactive compounds were shown to potentially be BBB-permeants with good pharmacological characteristics, except for ACL17 and ACL18 bioactive compounds. Standard inhibitor indicated two binding pockets within the protein, and all BBB-permeants bound to any of the two pockets. The PNZ had docking values of -6.8 and -6.0 kcal/mol at the pockets; whereas the ACL had docking values ranging from -6.7 to -4.6 kcal/mol. ACL similarly interacted with MAO as the PNZ, indicating that they are competitive inhibitors and therapeutics. We reported a step forward in the discovery of greener neuroprotective drugs and their molecular mechanisms to combat neurodegenerative illnesses.