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

• Published in: Life (Basel, Switzerland) Vol. 12; no. 11; p. 1764
• Main Authors: Rahman, M D Hasanur, Biswas, Partha, Dey, Dipta, Hannan, Md Abdul, Sahabuddin, Md, Araf, Yusha, Kwon, Youngjoo, Emran, Talha Bin, Ali, Md Sarafat, Uddin, Md Jamal
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-11-2022; MDPI
• Subjects: Anti-inflammatory drugs; Binding sites; Biocompatibility; Bioflavonoids; Care and treatment; chronic kidney disease; Computer applications; Cytokines; Diabetes; Drug development; Epicatechin; Fibrosis; Flavones; Flavonoids; Growth factors; Health aspects; Hypoglycemic agents; Identification and classification; Inflammation; Isoflavones; Kidney diseases; kidney fibrosis; Kidneys; Kinases; Lead compounds; Ligands; Molecular docking; Molecular dynamics; Pharmaceutical industry; Pharmaceutical research; pharmacokinetics; Physiological aspects; Phytochemicals; Plants; Proteins; Side effects; Signaling; TGFβR-1; Toxicity; Transforming growth factor-b; Transforming growth factors; Bangladesh; molecular dynamics simulations; chronic kidney disease; molecular docking; pharmacokinetics; TGFβR-1; flavonoids; kidney fibrosis
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life12111764

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,
and
studies are recommended to support the current findings.