Exploring the antidiabetic potential of phytoconstituents from Murraya koenigii: A molecular docking approach

Diabetes mellitus involves multiple metabolic dysfunctions, necessitating therapeutic agents capable of targeting several pathways simultaneously. The present study evaluated the antidiabetic potential of 71 phytoconstituents through molecular docking against three key targets: PPARγ, α-amylase (4W93) , and SGLT2 . Docking results revealed that selected compounds displayed strong affinity toward all three proteins, mahanine, ginsenoside Rd, naringin, and murrayacinine emerging as top-binding ligands. Mahanine showed the strongest interaction with PPARγ (–10.5 kcal/mol), supported by extensive hydrogen bonding, π-interactions, and hydrophobic contacts. Ginsenoside Rd demonstrated the highest affinity toward both α-amylase and SGLT2 (–10.1 kcal/mol) showing multiple stabilizing interactions within their active sites. Few other phytochemicals, such as mahanimbine, cyclomahanimbine, girinimbine, koenigine, and panaxatriol, also exhibited favorable binding orientations. ADMET and drug-likeness screening showed that carbazole alkaloids (mahanine, murrayacinine, mahanimbine, cyclomahanimbine, koenigine) possessed optimal molecular weight, moderate polarity, high predicted GI absorption, and minimal violations of Lipinski, Veber, Ghose, Egan, and Muegge filters. Conversely, naringin and ginsenosides , despite strong docking affinities, exhibited multiple rule violations and low predicted oral bioavailability due to their high molecular complexity and polarity. Overall, the combined docking and ADMET findings indicate that Murraya koenigii –derived carbazole alkaloids—particularly mahanine —represent promising multitarget antidiabetic lead molecules that can modulate insulin sensitivity, inhibit carbohydrate digestion, and reduce renal glucose reabsorption. These results warrant further in vitro, in vivo, and pharmacokinetic investigations to validate their therapeutic potential and advance them toward drug development.