An In Silico Molecular Modelling-Based Prediction of Potential Keap1 Inhibitors from Hemidesmus indicus (L.) R.Br. against Oxidative-Stress-Induced Diseases

被引：9

作者：

Vellur, Senthilkumar ^{[1
]}

Pavadai, Parasuraman ^{[2
]}

Babkiewicz, Ewa ^{[3
,4
]}

Pandian, Sureshbabu Ram Kumar ^{[1
]}

Maszczyk, Piotr ^{[3
]}

Kunjiappan, Selvaraj ^{[1
]}

机构：

[1] Kalasalingam Acad Res & Educ, Dept Biotechnol, Krishnankoil 626126, India

[2] MS Ramaiah Univ Appl Sci, Fac Pharm, Dept Pharmaceut Chem, Bengaluru 560054, India

[3] Univ Warsaw, Fac Biol, Dept Hydrobiol, PL-02089 Warsaw, Poland

[4] Univ Warsaw, Biol & Chem Res Ctr, PL-02089 Warsaw, Poland

来源：

MOLECULES | 2023年 / 28卷 / 11期

关键词：

oxidative stress; Hemidesmus indicus (L.) R.Br; Keap1-Nrf2; molecular docking; antioxidant; ANTIOXIDANT ACTIVITY; DISCOVERY; DYNAMICS; POWER;

D O I：

10.3390/molecules28114541

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The present study investigated the antioxidant potential of aqueous methanolic extracts of Hemidesmus indicus (L.) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this plant extract was assessed via antioxidant assays (DPPH, ABTS radical scavenging, and FRAP). Furthermore, 69 phytocompounds in total were derived from this plant using the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen 69 phytocompounds were docked against the Kelch-Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 angstrom) along with the standard drug (CPUY192018). H. indicus (L.) R.Br. extract (100 mu g x mL(-1)) showed 85 +/- 2.917%, 78.783 +/- 0.24% of DPPH, ABTS radicals scavenging activity, and 161 +/- 4 mu g x mol (Fe (II)) g(-1) ferric ion reducing power. The three top-scored hits, namely Hemidescine (-11.30 Kcal x mol(-1)), Beta-Amyrin (-10.00 Kcal x mol(-1)), and Quercetin (-9.80 Kcal x mol(-1)), were selected based on their binding affinities. MD simulation studies showed that all the protein-ligand complexes (Keap1-HEM, Keap1-BET, and Keap1-QUE) were highly stable during the entire simulation period, compared with the standard CPUY192018-Keap1 complex. Based on these findings, the three top-scored phytocompounds may be used as significant and safe Keap1 inhibitors, and could potentially be used for the treatment of oxidative-stress-induced health complications.

引用

页数：24