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An In-Silico Identification of Potential Flavonoids against Kidney Fibrosis Targeting TGF beta R-1
- Title
- An In-Silico Identification of Potential Flavonoids against Kidney Fibrosis Targeting TGF beta R-1
- Authors
- Rahman, Md Hasanur; Biswas, Partha; Dey, Dipta; Hannan, Md Abdul; Sahabuddin, Md; Araf, Yusha; Kwon, Youngjoo; Bin Emran, Talha; Ali, Md Sarafat; Uddin, Md Jamal
- Ewha Authors
- 권영주
- SCOPUS Author ID
- 권영주
- Issue Date
- 2022
- Journal Title
- LIFE-BASEL
- ISSN
- 2075-1729
- Citation
- LIFE-BASEL vol. 12, no. 11
- Keywords
- kidney fibrosis; chronic kidney disease; TGF beta R-1; flavonoids; pharmacokinetics; molecular docking; molecular dynamics simulations
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Fibrosis is a hallmark of progressive kidney diseases. The overexpression of profibrotic cytokine, namely transforming growth factor beta (TGF-beta) due to excessive inflammation and tissue damage, induces kidney fibrosis. The inhibition of TGF-beta signaling is markedly limited in experimental disease models. Targeting TGF-beta signaling, therefore, offers a prospective strategy for the management of kidney fibrosis. Presently, the marketed drugs have numerous side effects, but plant-derived compounds are relatively safer and more cost-effective. In this study, TGF beta R-1 was targeted to identify the lead compounds among flavonoids using various computational approaches, such as ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analysis, molecular docking, and molecular dynamics simulation. ADME/T screening identified a total of 31 flavonoids with drug-like properties of 31 compounds, a total of 5 compounds showed a higher binding affinity to TGF beta R-1, with Epicatechin, Fisetin, and Luteolin ranking at the top three (-13.58, -13.17, and -10.50 kcal/mol, respectively), which are comparable to the control drug linagliptin (-9.074 kcal/mol). The compounds also exhibited outstanding protein-ligand interactions. The molecular dynamic simulations revealed a stable interaction of these compounds with the binding site of TGF beta R-1. These findings indicate that flavonoids, particularly Epicatechin, Fisetin, and Luteolin, may compete with the ligand-binding site of TGF beta R-1, suggesting that these compounds can be further evaluated for the development of potential therapeutics against kidney fibrosis. Further, in-vitro and in-vivo studies are recommended to support the current findings.
- DOI
- 10.3390/life12111764
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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