Molecular Docking and ADMET-Based Discovery of Glycyrrhiza glabra Bioactives as P-Glycoprotein Inhibitors for Combating Multidrug Resistance
نویسندگان
1 Department of Regulatory Affairs, Hikma Pharmaceuticals USA Inc.,2 Esterbrook Lane, Cherry Hill, NJ 08003, USA
2 Department of Pharmacy Practice, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad U.P, 244001, India
3 KL Business School, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, Andhra Pradesh 522502, India
4 Department of Pharmaceutics, Malla Reddy Institute of Pharmaceutical Sciences, Malla Reddy Vishwavidyapeeth (Deemed to be University), Secunderabad, 500100, Telangana, India
5 Department of Pharmacy Practice, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai 600 117, India
6 Department of Pharmacology, Arulmigu Kalasalingam College of Pharmacy, Krishnankoil, Viridhunagar Dist., Tamil Nadu, India
7 School of Pharmacy, ITM University, Gwalior, Madhya Pradesh, India
8 Department of Regulatory Affairs, Ricon Pharma LLC, 100 Ford Rd, Suite #9, Denville, NJ 07834, USA
doi
10.48309/ajca.2026.553659.1952چکیده
This study employed an extensive computational approach to identify bioactive compounds from Glycyrrhiza glabra (licorice) with potential inhibitory activity against P-glycoprotein (P-gp), a key efflux transporter associated with multidrug resistance (MDR) in cancer. Twenty phytochemicals, including triterpenoid saponins, flavonoids, and chalcones, were evaluated using molecular docking and in silico ADMET analyses. Docking studies using AutoDock Vina against the human P-gp structure (PDB ID: 7O9W) revealed several compounds exhibiting stronger binding affinities than the standard inhibitor verapamil (–7.8 kcal/mol). Among them, 18β-glycyrrhetinic acid (–9.7 kcal/mol), glabridin (–9.3 kcal/mol), glabranin (–9.1 kcal/mol), and licoflavone A (–8.7 kcal/mol) showed the most stable interactions with key residues PHE343, GLN347, GLU875, and TYR310, crucial for substrate recognition and transport inhibition. ADMET analyses indicated that glabridin, glabranin, and licoflavone A possess high gastrointestinal absorption, non-hepatotoxicity, and favorable oral bioavailability, satisfying Lipinski and Veber’s drug-likeness criteria. Conversely, glycosylated saponins displayed lower permeability, but minimal toxicity, suggesting potential combinatorial benefits. Overall, glabridin, glabranin, and licoflavone A have emerged as promising natural P-gp inhibitors capable of reversing MDR in cancer, meriting further in vitro and in vivo validation.
