Computational investigation of Plectranthus neochilus essential oil phytochemicals interaction with dipeptidyl peptidase 4: A potential avenue for antidiabetic drug discovery
Mamoudou Hamadou, Alassane Abdoulaye, Nganso Yves Oscar Ditchou, Jairus Olumasai Nandwa, Raimi Mouhamed Zakiou Kolawole Adissa, Martin Alain Mune Mune
Abstract
This study explores the antidiabetic potential of essential oil compounds from Plectranthus neochilus through molecular docking and pharmacological analysis targeting dipeptidyl peptidase-4 (DPP-4), a key enzyme in type 2 diabetes management. Citronellyl butyrate exhibited the highest binding affinity (−7.3 kcal/mol), followed by citronellol (−7.2 kcal/mol), citronellyl formate (−7.1 kcal/mol), and linalool (−6.7 kcal/mol), indicating strong inhibitory potential against DPP-4. Molecular interactions revealed that citronellol forms hydrogen bonds with Asp709 and Lys122, alongside π-π interactions with Phe240, enhancing binding stability. Citronellyl butyrate demonstrated favorable pharmacokinetic properties, including high gastrointestinal absorption (logP: 4.03), blood-brain barrier permeability, and moderate CYP2C9 inhibition, aligning with Lipinski’s Rule of Five. Citronellol showed high gastrointestinal absorption (68 %) and moderate blood-brain barrier penetration (36.13 %), with a moderate bioavailability, warrants further investigation. Toxicity profiles indicated low acute oral toxicity (LD50: 1.81 and 2.03 -log(mol/kg) for citronellyl butyrate and citronellol, respectively) and moderate risks for drug-induced liver injury (44.81 % and 45.4 %) and mutagenicity (36.35 % and 39.39 %). α-terpineol and isomenthone exhibited good absorption (log P: 2.49 and 2.60) and low metabolic interaction risks, supporting their therapeutic potential. These findings highlight the potential of P. neochilus essential oil compounds as natural DPP-4 inhibitors, offering a novel approach to diabetes management.