Next Article in Journal
Arylsulfonylamino-Benzanilides as Inhibitors of the Apical Sodium-Dependent Bile Salt Transporter (SLC10A2)
Previous Article in Journal
Application and Analysis of the Folin Ciocalteu Method for the Determination of the Total Phenolic Content from Limonium Brasiliense L.
Article Menu

Export Article

Open AccessArticle
Molecules 2013, 18(6), 6866-6882; doi:10.3390/molecules18066866

Design, Synthesis and Evaluation of the Antibacterial Enhancement Activities of Amino Dihydroartemisinin Derivatives

1
Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing 400038, China
2
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
3
Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
*
Author to whom correspondence should be addressed.
Received: 14 May 2013 / Revised: 29 May 2013 / Accepted: 30 May 2013 / Published: 10 June 2013
Download PDF [736 KB, 18 June 2014; original version 18 June 2014]

Abstract

Artemisinin (ART) and its derivatives artesunate (AS), dihydroartemisinin (DHA) are a group of drugs containing a sesquiterpene lactone used to treat malaria. Previously, AS was shown to not have antibacterial activity but to significantly increase the antibacterial activities of β-lactam antibiotics against E. coli. Herein, molecular docking experiments showed that ART, AS and DHA could dock into AcrB very well, especially DHA and AS; both DHA and AS had the same docking pose. The affinity between AS and AcrB seemed weaker than that of DHA, while the succinate tail of AS, which was like a “bug”, could extend in the binding pocket very well. Imitating the parent nucleus of DHA and the succinate tail of AS, twenty-one DHA derivatives 4au were designed and synthesized. Among them, seventeen were new compounds. The synergistic effects against E. coli AG100A/pET28a-AcrB showed among the new structures 4k, 4l, 4m, 4n, and 4r exhibited significant synergism with β-lactam antibiotics although they had no direct antibacterial activities themelves. The bacterial growth assay showed that only 4k in combination with ampicillin or cefuroxime could totally inhibit bacterial growth from 0 to 12 h, demonstrating that 4k had the best antibacterial enhancement effect. In conclusion, our results provided a new idea and several candidate compounds for antibacterial activity enhancers against multidrug resistant E. coli.
Keywords: dihydroartemisinin; derivatives; antibiotic resistance; antibacterial activity; synergistic effect; β-lactam antibiotic dihydroartemisinin; derivatives; antibiotic resistance; antibacterial activity; synergistic effect; β-lactam antibiotic
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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

Wu, C.; Liu, J.; Pan, X.; Xian, W.; Li, B.; Peng, W.; Wang, J.; Yang, D.; Zhou, H. Design, Synthesis and Evaluation of the Antibacterial Enhancement Activities of Amino Dihydroartemisinin Derivatives. Molecules 2013, 18, 6866-6882.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top