Liew, Sook Yee and Sivasothy, Yasodha and Shaikh, Nimra Naveed and Isa, Diyana Mohd and Lee, Vannajan Sanghiran and Choudhary, M. Iqbal and Awang, Khalijah (2020) beta-Glucuronidase inhibitors from Malaysian plants. Journal of Molecular Structure, 1221. ISSN 0022-2860, DOI https://doi.org/10.1016/j.molstruc.2020.128743.
Full text not available from this repository.Abstract
Toxic metabolites that could promote the formation of tumors are generated with high levels of beta-glucuronidase activities. Hence, the inhibition of the beta-glucuronidase enzyme is effective in the prevention of colonic carcinogenesis, and other diseases. This study aims to investigate the beta-glucuronidase inhibitory effect of compounds that were isolated from Nauclea subdita (Korth.) Steud. and Alpinia pahangensis Ridley, together with their mode of inhibition, and their interactions with the enzyme. Angustine (1) and (E)-labda-8 (17),12-dien-15,16-dial (2) are secondary metabolites which were isolated from Nauclea subdita (Korth.) Steud. and Alpinia pahangensis Ridley, respectively. Both exhibited potent inhibitory activities against the beta-glucuronidase enzyme with IC50 values of 5.6 +/- 0.70 and 23.61 +/- 3.32 mu M, respectively. The enzyme kinetic studies suggested that compounds 1 and 2 were noncompetitive inhibitors with inhibition constants (Ki) of 8.46 and 22.0 mu M, respectively. In silico molecular docking and molecular dynamics simulation studies showed that the amino acid residues that interacted with compounds 1 and 2 were Phe161, Leu361, Phe448, Tyr468, Tyr472, and Leu561. These amino acid residues interacted with compound 1 with lower energy as compared to compound 2. Furthermore, the binding free energy of compound 1 (GBTOT value of -31.69 kcal mol(-1)) was found to be lower than that of compound 2 (GBTOT value of -22.32 kcal mol(-1)). Compound 1 was thus predicted to be a more active inhibitor through in silico molecular docking and molecular dynamics simulation studies. (C) 2020 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Angustine; (E)-labda-8(17),12-dien-15,16-dial; beta-Glucuronidase; Molecular docking; Molecular dynamics simulations |
| Subjects: | Q Science > Q Science (General) Q Science > QD Chemistry |
| Divisions: | Centre for Foundation Studies in Science Centre for Foundation Studies in Science > Chemistry Division Faculty of Science Faculty of Science > Department of Chemistry |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 29 Nov 2023 01:38 |
| Last Modified: | 29 Nov 2023 04:35 |
| URI: | http://eprints.um.edu.my/id/eprint/36189 |
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