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Computational screening of phytocompound isolated from the plant Toddalia asiatica and Coleonema album as potential inhibitors against enzyme DPP-4 as a treatment for Type-2 Diabetes mellitus

Raje Siddiraju Upendra, Sanjay Srinivas Nagar, and Karthick Vasudevan

School of Electronics and Communication Engineering, REVA University, Bangalore, India

Received: 28 June 2023 Accepted: 12 November 2023

Abstract:

Human hormone glucagon-like peptide-1 (GLP-1) lowers α-cell glucagon and increases β-cell insulin. GLP-1 is digested by dipeptidyl peptidase (DPP-4) enzyme; hence, the inhibition of DPP-4 enzyme prevents the digestion of GLP-1 and reduces the occurrence of type 2 diabetes condition. Present study developed a database consists of 1837 molecules structurally similar to selected query compounds applying PubChem screening and was further screened for drug-likeness and ADME/T behaviour using SwissADME tool. Total of six compounds, i.e. Toddalolactone, Ulopterol, 1-O-methyl 4-O-(2-oxo-1H-quinolin-4-yl) butanedioate, [2-oxo-3-(3-oxobutyl)-1H-quinolin-4-yl] acetate, N-(2,5-Dioxo-5,6-dihydro-2H-pyrano[3,2-c]quinolin-3-yl)acetamide, (2S)-2-amino-2-phenyl-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4] triazolo [4,3-a]1yrazine-7-yl] ethanone cleared screening and were tested for DPP-4 enzyme inhibitory activity comparing Alogliptin as standard drug applying AutoDock in silico approach (Argus Lab, Discovery Studio and PyMol). All the six compounds displayed RMSD values less than 2A⁰, and binding energies of − 8.5139 kcal/mol, − 9.438 kcal/mol, − 9.4783 kcal/mol, − 8.898 kcal/mol, − 9.022 kcal/mol, and − 7.604 kcal/mol, respectively. Study testified that Toddalolactone isolated from the plant Toddalia asiatica (− 8.5139 kcal/mol) confers 03 hydrogen bonds, 03 Pi-Pi stack bonds and RMSD values of 0.281 A⁰, phytocompound Ulopterol (− 9.438 kcal/mol) isolated from the plant Coleonema album, interacted with 04 amino acids of DPP-4 enzyme active site conferring stable hydrogen (02) and Pi-Pi bonds (02) with RMSD value 0.78 A⁰, represents increased DPP-4 enzyme inhibitory activity in comparison with standard drug Alogliptin binding energy of − 7.34 kcal/mol with only 02 interactive bonds. It is evidenced from the study that a higher number of bonds indicates the stability of the complex formed with increased enzyme inhibitory activity; hence, the phytocompound Toddalolactone derived from the plant Toddalia asiatica and Ulopterol from Coleonema album as a potential lead molecule shall be tested further resulting in in vitro and in vivo procedures in order to develop novel drugs in the treatment of Type 2 Diabetes mellitus condition.

Keywords: Type 2 Diabetes mellitus; Dipeptidyl peptidase (DPP-4); Toddalia asiatica; Toddalolactone Coleonema album; Ulopterol; Alogliptin; Molecular docking

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-03209-0

Chemical Papers 78 (3) 1833–1847 (2024)