Computational Drug Design Approaches for the Identification of Novel Antidiabetic Compounds from Natural Resources through Molecular Docking, ADMET, and Toxicological Studies.

Autor: Akter B; Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, Bangladesh.; Pharmaceutical Sciences Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, Bangladesh., Uddin MS; Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, Bangladesh.; Department of Pharmacy, University of Science and Technology, Chittagong, Bangladesh., Islam MR; Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, Bangladesh., Ahamed KU; Pharmaceutical Sciences Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, Bangladesh., Aktar MN; School of Natural Sciences, Macquarie University, Sydney, NSW, 2109, Australia., Hossain MK; Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong, Bangladesh. mkhossain73@yahoo.com., Salamatullah AM; Department of Food Science & Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia., Bourhia M; Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences, , Ibn Zohr University, Agadir, Morocco.
Jazyk: angličtina
Zdroj: Cell biochemistry and biophysics [Cell Biochem Biophys] 2024 Oct 08. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.1007/s12013-024-01540-1
Abstrakt: Type 2 diabetes mellitus (T2DM) is usually depicted by relative insulin deficiency, raised blood glucose levels, and the predominant risk factor, insulin resistance. Hence, the development of insulin sensitizer drugs targeting PPAR-γ receptors has expanded enormous interest as an attractive choice for T2DM treatment. Thiazolidinediones (TZD) enhance insulin sensitivity either by directly functioning on gene transcription of the PPARγ receptor related to glucose homeostasis or by systemic sensitization of insulin and, therefore, improved hyperglycemia in a wide range of patients. However, severe complications and adverse effects of TZDs necessitate the development of an efficacious and reliable insulin sensitizer from alternative resources. On the contrary, Nature is a rich source of anticipated effective and safer medicine; more than fifty percent of drugs on the market are developed from natural products. Hence, searching for a new PPAR-γ agonist from bioactive secondary compounds of medicinal plants along with greater efficacy and safety is a recognized and consistent tactic for developing novel antidiabetic agents. Pulicaria jaubertii is a fragrant perennial aromatic plant with anti-inflammatory, antidiabetic, antimicrobial, antimalarial, and insecticidal properties. The current study was designed to use a computer-aided drug design to explore the best antidiabetic compounds from P. jaubertii. Herein, the molecular docking study of 80 investigated ligands against the PPAR-γ receptor identifies the highest docking score for five ligands ranging from -8.9 kcal/mol to 8.0 kcal/mol, which is also more significant than the standard drug pioglitazone (-7.7 kcal/mol) determined by the PyRx 8.0 virtual screening software. GLN286, CYS285, SER289, TYR473, MET364, ARG288, ILE341, and LEU333 residues are found to be significant contributors to the non-bonded interaction between ligands and receptors. Molecular electrostatic potential (MEP), DFT, molecular orbital (MO), ADMET, and toxicological analyses were performed on the selected five high-scored ligands of P. jaubertii. Results documented that all investigated ligands, especially L4, show considerably excellent profiles in molecular docking, MEP, DFT, MO, ADMET, and toxicological predictions, suggesting our drug-designing approaches may contribute to the development of a novel antidiabetic drug for the treatment of T2DM from natural resources.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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