GC-MS- and NMR-based metabolomics and molecular docking reveal the potential alpha-glucosidase inhibitors from psychotria malayana jack Leaves

Nipun, Tanzina Sharmin and Khatib, Alfi and Ibrahim, Zalikha and Ahmed, Qamar Uddin and Redzwan, Irna Elina and Primaharinastiti, Riesta and Saiman, Mohd Zuwairi and Fairuza, Raudah and Widyaningsih, Tri Dewanti and AlAjmi, Mohamed F and Khalifa, Shaden A. M. and El-Seedi, Hesham (2021) GC-MS- and NMR-based metabolomics and molecular docking reveal the potential alpha-glucosidase inhibitors from psychotria malayana jack Leaves. Pharmaceuticals, 14 (10). pp. 1-29. ISSN 1424-8247

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Abstract

Psychotria malayana Jack leaf, known in Indonesia as “daun salung”, is traditionally used for the treatment of diabetes and other diseases. Despite its potential, the phytochemical study related to its anti-diabetic activity is still lacking. Thus, this study aimed to identify putative inhibitors of alpha-glucosidase, a prominent enzyme contributing to diabetes type 2 in P. malayana leaf extract using gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabolomics, and to investigate the molecular interaction between those inhibitors and the enzyme through in silico approach. Twenty samples were extracted with different solvent ratios of methanol–water (0, 25, 50, 75, and 100% v/v). All extracts were tested on the alpha-glucosidase inhibition (AGI) assay and analyzed using GC-MS and NMR. Multivariate data analysis through a partial least square (PLS) and orthogonal partial square (OPLS) models were developed in order to correlate the metabolite profile and the bioactivity leading to the annotation of the putative bioactive compounds in the plant extracts. A total of ten putative bioactive compounds were identified and some of them reported in this plant for the first time, namely 1,3,5-benzenetriol (1); palmitic acid (2); cholesta-7,9(11)-diene-3-ol (3); 1-monopalmitin (4); b-tocopherol (5); a-tocopherol (6); 24-epicampesterol (7); stigmast-5-ene (8); 4-hydroxyphenylpyruvic acid (10); and glutamine (11). For the evaluation of the potential binding modes between the inhibitors and protein, the in silico study via molecular docking was performed where the crystal structure of Saccharomyces cerevisiae isomaltase (PDB code: 3A4A) was used. Ten amino acid residues, namely ASP352, HIE351, GLN182, ARG442, ASH215, SER311, ARG213, GLH277, GLN279, and PRO312 established hydrogen bond in the docked complex, as well as hydrophobic interaction of other amino acid residues with the putative compounds. The alpha-glucosidase inhibitors showed moderate to high binding affinities (-5.5 to -9.4 kcal/mol) towards the active site of the enzymatic protein, where compounds 3, 5, and 8 showed higher binding affinity compared to both quercetin and control ligand.

Item Type:	Article (Journal)
Additional Information:	6915/93038
Uncontrolled Keywords:	P. malayana; a-glucosidase; multivariate data analysis; GC-MS; NMR; molecular docking
Subjects:	Q Science > Q Science (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry Kulliyyah of Pharmacy
Depositing User:	Dr. Alfi Khatib
Date Deposited:	15 Oct 2021 08:57
Last Modified:	15 Oct 2021 08:57
URI:	http://irep.iium.edu.my/id/eprint/93038

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