Pharmacoinformatics-based prediction of Checkpoint kinase-1 inhibitors from Momordica charantia Linn. for cancer
Checkpoint kinase 1 (Chk-1), a serine/threonine kinase, is a key regulator of cell cycle arrest and a promising target in cancer research. This study aimed to identify potential Chk-1 inhibitors from Momordica charantia Linn. using high-throughput molecular docking and a graph theoretical network approach to determine Chk-1 as the target protein.
Among 86 compounds identified from M. charantia L., five—α-spinasterol (-9.7 kcal/mol), stigmasterol (-9.6 kcal/mol), stigmasta-7,22,25-trienol (-9.5 kcal/mol), campesterol (-9.5 kcal/mol), and stigmasta-7,25-dien-3β-ol (-9.5 kcal/mol)—exhibited the highest binding affinity for Chk-1, outperforming the standard Chk-1 inhibitor CCT245737 (-8.3 kcal/mol). Pharmacokinetic analyses confirmed these compounds possess non-toxic, drug-like properties.
Molecular dynamics (MD) simulations further validated the strong intermolecular interactions and stability of these compounds with Chk-1. Additionally, binding free-energy estimates from molecular docking were corroborated by Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) calculations from MD simulation trajectories.
Collectively, these five compounds demonstrate strong potential as Chk-1 inhibitors and could serve as promising candidates for the development of novel cancer therapies.