LC-MS-based metabolomics and molecular docking to characterize α-glucosidase inhibitors from Psychotria Malayana Jack leaves extract

• Main Authors: Nipun, Tanzina Sharmin, Khatib, Alfi, Ibrahim, Zalikha, Ahmed, Qamar Uddin, Redzwan, Irna Elina
• Format: Conference or Workshop Item
• Language: English; English; English; English
• Published: 2021
• Subjects: Q Science (General)
• Online Access: http://irep.iium.edu.my/98294/1/1343996-Abstract%20for%20ASMPS%20%282021%29.pdf; http://irep.iium.edu.my/98294/2/1343998-Schedule%20of%20Scientific%20Program%20Oral%20Presentation%201%20August%202021.pdf; http://irep.iium.edu.my/98294/3/1343997-National%20Conference%20Certificate%20%28ASMPS%202021%29%20%28Oral%20presentation%29.pdf; http://irep.iium.edu.my/98294/5/98294_LC-MS-based%20metabolomics%20and%20molecular%20docking.pdf; http://irep.iium.edu.my/98294/

The plant Psychotria malayana Jack belongs to the Rubiaceae family and is locally referred to as "meroyan sakat/salung" in Malaysia. Diabetes has traditionally been treated with P. malayana Jack. Despite its potential, scientific evidence for this plant is still lacking. Thus, the current study sought to investigate α�glucosidase inhibitors in P. malayana leaf extracts using a metabolomics approach, as well as to illuminate ligand-protein interactions using in-silico techniques (molecular docking). The plant leaves were extracted in five different ratios with methanol and water (100, 75, 50, 25 and 0% v/v; water–methanol). After testing for α-glucosidase inhibition activity, each extract was analyzed using liquid chromatography tandem to mass spectrometry. Additionally, the data were subjected to multivariate data analysis by developing an orthogonal partial least squares method in order to establish a correlation between the chemical profile and the bioactivity. The loading plots demonstrated that the m/z signals correspond to the activity of α-glucosidase inhibitors, allowing five putative bioactive compounds to be identified, namely 1-monopalmitin (1), 5′-hydroxymethyl-1′-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1′-one (2), α-terpinyl-β-glucoside (3), machaeridiol-A (4), and 4-hydroxyphenylpyruvic acid (5). The discovered inhibitors were docked against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A) using the Auto Dock Vina software. Nine hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, HIE351, ASH215, and GLU411. Compound 1, 2, 3, 4, and 5 showed binding affinity values of −6.1, −8.3, −7.6, −10.0, and −6.5 kcal/mol, respectively, indicating the moderate to the good binding affinity of the compounds towards the active site of the enzyme when compared to that of a known α-glucosidase inhibitor, quercetin (−8.4 kcal/mol). The five identified compounds showing potential binding affinity towards the α-glucosidase enzyme in in-silico study could be the bioactive compounds associated with this plant's traditional use.