In Silico Investigation of Aporphine Alkaloids Isolated From Magnolia coriacea Against α-Glucosidase and Tyrosine Phosphatase 1B

Abstract

Objective Magnolia coriacea is a rare species of Magnoliaceae and categorized as critically endangered, yet known for its valuable pharmaceutical properties. Phytochemical study of the plant was carried out, and the isolated compounds were subjected to different computational platforms to predict their chemical, inhibitory, physicochemical, and pharmacological properties. Methods M coriacea dried twig or leaf powder was partially extracted with n-hexane, ethyl acetate, and 90% methanol to produce the corresponding extracts, which were subjected to column chromatography. The isolated compounds were identified by nuclear magnetic resonance (NMR) spectroscopic and electrospray ionization mass spectrometry (ESI-MS) methods. Results Eight known aporphine alkaloids were isolated, (+)-glaucine N-oxide (1), N-methyl glaucine acetate (2), (+)-( S)-glaucine (3), magnoflorine (4), pontevedrine (5), O-methylatheroline (6), 7-hydroxydehydroglaucine (7), and mangochinine acetate (8). Quantum-based calculations found no abnormal structural constraints and suggested 2, 4, and 8 as the most promising inhibitors of protein structures in general with intensive nucleophilic reactive sites at their nitrogen atoms. Classical-based docking simulation agrees with this with respect to 3W37 (docking score [DS] < −12 kcal·mol−1) and PTP1B (DS ca −13 kcal·mol−1) structures. The biocompatibility and pharmacokinetics of the three candidates given by quantitative structure–activity relationship (QSAR) and absorption, distribution, metabolism, excretion, and toxicity (ADMET) regressions justify their potential for medicinal development. The results encourage further experimental studies of the promising M coriacea-extracted aporphine alkaloids for drug-developing purposes, especially mangochinine acetate (8). Conclusions Isolation and molecular docking simulation of 8 aporphine alkaloids were accomplished. QSAR and ADMET regressions suggested that three compounds (2, 4, and 8) were the most suitable for medicinal applications given both biocompatibility and pharmacokinetics based on specific prediction toward 3W37 (α-glucosidase) and PTP1B (tyrosine phosphatase 1B) structures.