Next Article in Journal
Ionogels Based on Poly(methyl methacrylate) and Metal-Containing Ionic Liquids: Correlation between Structure and Mechanical and Electrical Properties
Next Article in Special Issue
TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation
Previous Article in Journal
De novo Transcriptome Generation and Annotation for Two Korean Endemic Land Snails, Aegista chejuensis and Aegista quelpartensis, Using Illumina Paired-End Sequencing Technology
Previous Article in Special Issue
Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(3), 389; doi:10.3390/ijms17030389

Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening

1
Beijing Key Lab of Traditional Chinese Medicine (TCM) Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
2
Key Laboratory of TCM-Information Engineer of State Administration of TCM, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China
3
Department of Chemistry, Capital Normal University, Beijing 100069, China
*
Author to whom correspondence should be addressed.
Academic Editors: Ge Zhang and Aiping Lu
Received: 23 January 2016 / Revised: 25 February 2016 / Accepted: 4 March 2016 / Published: 16 March 2016
View Full-Text   |   Download PDF [2694 KB, uploaded 16 March 2016]   |  

Abstract

Endothelin-1 receptors (ETAR and ETBR) act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional Chinese herbs. Ligand- and structure-based virtual screening was performed to screen an in-house database of traditional Chinese herbs, followed by a series of in vitro bioassay evaluation. Aristolochic acid A (AAA) was first confirmed to be a dual ETA/ETB receptor antagonist based intracellular calcium influx assay and impedance-based assay. Dose-response curves showed that AAA can block both ETAR and ETBR with IC50 of 7.91 and 7.40 μM, respectively. Target specificity and cytotoxicity bioassay proved that AAA is a selective dual ETA/ETB receptor antagonist and has no significant cytotoxicity on HEK293/ETAR and HEK293/ETBR cells within 24 h. It is a feasible and effective approach to discover bioactive compounds from traditional Chinese herbs using in silico screening combined with in vitro bioassay evaluation. The structural characteristic of AAA for its activity was especially interpreted, which could provide valuable reference for the further structural modification of AAA. View Full-Text
Keywords: dual ETA/ETB receptor; pharmacophore; molecular docking; aristolochic acid A; bioassay evaluation dual ETA/ETB receptor; pharmacophore; molecular docking; aristolochic acid A; bioassay evaluation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, X.; Zhang, Y.; Liu, Q.; Ai, Z.; Zhang, Y.; Xiang, Y.; Qiao, Y. Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening. Int. J. Mol. Sci. 2016, 17, 389.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top