An In-Silico Identification of Potential Flavonoids against Kidney Fibrosis Targeting TGF beta R-1
- 주제(키워드) kidney fibrosis , chronic kidney disease , TGF beta R-1 , flavonoids , pharmacokinetics , molecular docking , molecular dynamics simulations
- 주제(기타) Biology; Microbiology
- 설명문(일반) [Rahman, Md Hasanur; Biswas, Partha; Dey, Dipta; Hannan, Md Abdul; Uddin, Md Jamal] ABEx Biores Ctr, Dhaka 1230, Bangladesh; [Rahman, Md Hasanur; Sahabuddin, Md; Ali, Md Sarafat] Bangabandhu Sheikh Mujibur Rahman Sci & Technol U, Dept Biotechnol & Genet Engn, Fac Life Sci, Gopalganj 8100, Bangladesh; [Biswas, Partha] Jashore Univ Sci & Technol, Lab Pharmaceut Biotechnol & Bioinformat, Dept Genet Engn & Biotechnol, Jashore 7408, Bangladesh; [Dey, Dipta] Bangabandhu Sheikh Mujibur Rahman Sci & Technol U, Fac Life Sci, Dept Biochem & Mol Biol, Gopalganj 8100, Bangladesh; [Hannan, Md Abdul] Bangladesh Agr Univ, Dept Biochem & Mol Biol, Mymensingh 2202, Bangladesh; [Araf, Yusha] Shahjalal Univ Sci & Technol, Sch Life Sci, Dept Genet Engn & Biotechnol, Sythet 3114, Bangladesh; [Kwon, Youngjoo; Uddin, Md Jamal] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea; [Bin Emran, Talha] BGC Trust Univ Bangladesh, Dept Pharm, Chittagong 4381, Bangladesh; [Bin Emran, Talha] Daffodil Int Univ, Fac Allied Hlth Sci, Dept Pharm, Dhaka 1207, Bangladesh
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000203103
- 본문언어 영어
- Published As https://doi.org/10.3390/life12111764
- PubMed https://pubmed.ncbi.nlm.nih.gov/36362919
초록/요약
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.
more