An In-Silico Identification of Potential Flavonoids against Kidney Fibrosis Targeting TGFβR-1

MD Hasanur Rahman, Partha Biswas, Dipta Dey, Md Abdul Hannan, Md Sahabuddin, Yusha Araf, Youngjoo Kwon, Talha Bin Emran, Md Sarafat Ali, Md Jamal Uddin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Fibrosis is a hallmark of progressive kidney diseases. The overexpression of profibrotic cytokine, namely transforming growth factor β (TGF-β) due to excessive inflammation and tissue damage, induces kidney fibrosis. The inhibition of TGF-β signaling is markedly limited in experimental disease models. Targeting TGF-β 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, TGFβR-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 TGFβR-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 TGFβR-1. These findings indicate that flavonoids, particularly Epicatechin, Fisetin, and Luteolin, may compete with the ligand-binding site of TGFβR-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.

Original languageEnglish
Article number1764
JournalLife
Volume12
Issue number11
DOIs
StatePublished - Nov 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • TGFβR-1
  • chronic kidney disease
  • flavonoids
  • kidney fibrosis
  • molecular docking
  • molecular dynamics simulations
  • pharmacokinetics

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