Hecogenin a Plant Derived Small Molecule as an Antagonist to BACE-1: A Potential Target for Neurodegenerative Disorders

Abstract

The field of drug discovery has recognized the significance of computer-aided drug design. Recent advancements in structure identification and characterization, bio-computational science and molecular biology have significantly contributed to the development of novel treatments for various diseases. Alzheimer’s disease is prevalent in over 50 million affected people, with the pathological condition of amyloidal plaque formation by the beta-amyloidal peptide that results in lesions of the patient’s brain, thus making the target prediction and treatment a hurdle. In this study, we evaluated the potential of 54 bioactive compounds from Justicia adhatoda L. and Sida cordifolia L. identified through LC-MS/MS against the β-site amyloid precursor cleaving enzyme (beta-secretase) that results in the formation of amyloidal plaques. To study the drug-likeness of the phytocompounds, Lipinski’s rule of five for ADME profiling and toxicity prediction was performed. Molecular docking was performed using auto-dock tool of PyRx software; molecular dynamic simulations were performed using the Schrodinger suite. Molecular docking against BACE-1 protein revealed that hecogenin, identified from S. cordifolia has a broad spectrum of pharmacological applications and a binding affinity score of −11.3 kcal/Mol. The Hecogenin–BACE-1 protein complex was found to be stable after 30 ns of MD simulation, resulting in its substantial stability. Further studies focusing on the in vivo neuroprotective activity of hecogenin against the disease will pave the way for efficient drug discovery from natural sources in a precise manner.

Metabolomic Profiling of Leptadenia reticulata: Unveiling Therapeutic Potential for Inflammatory Diseases through Network Pharmacology and Docking Studies

“…To evaluate the drug-likeness of the compound various parameters were computed, including number of hydrogen bond donors and acceptors, molecular weight, molecule polar surface area, Veber's rule, the logarithm of the n-octanol/water partition coefficient(logP), and Lipinski's rule of five [40]. Additionally, ADMET prediction was carried out while considering elements including cytochrome P450(CYP) 2D6 inhibition, plasma membrane binding, blood-brain barrier penetration, aqueous solubility, and hepatotoxicity [16]. The ProTox II (https://tox-new.charite.de/; accessed on 2 October 2023) online server was used to calculate the LD50 value of the phytocompounds and to predict organ toxicity.…”

“…Medicinal plants yield a diverse array of secondary metabolites, including flavonoids, terpenoids, tannins, steroids, quinones, coumarins, and alkaloids. These compounds exhibit a broad spectrum of pharmacological properties [ 16 ]. Leptadenia reticulata is one of the traditional medicinal plants; it belongs to the family Apocynaceae [ 17 ].…”