Next Article in Journal
Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy
Previous Article in Journal
Polyphenolic Profile and Targeted Bioactivity of Methanolic Extracts from Mediterranean Ethnomedicinal Plants on Human Cancer Cell Lines
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(4), 402; doi:10.3390/molecules21040402

A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation

1
School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
2
Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 27 January 2016 / Revised: 16 March 2016 / Accepted: 21 March 2016 / Published: 24 March 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [1872 KB, uploaded 24 March 2016]   |  

Abstract

A series of oleanolic acid derivatives were synthesized by diverse reactions, including the introduction of conjugated alkadiene and epoxy ring moieties formed by means of photosensitized oxidation. Eosin Y was used as photosensitizer during this process. Next the cytotoxicity of the products was evaluated on HepG2.2.15 cells to determine the appropriate treatment concentration for the subsequent experiments. Most of the OA derivatives exhibited anti-HBV antigens secretion activity in HepG2.2.15 cells. Among the tested compounds, OA-4 (3.13 µg/mL) showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with inhibitory ratios of 90.52% ± 1.78%, 31.55% ± 3.65%, and 94.57% ± 3.11% after 6 days, respectively. Besides, OA-4 was further investigated in a duck model with DHBV infection. When OA-4 was administered at a dosage of 500 mg/kg, the results revealed a significant inhibitory effects of DHBV at 19.94% ± 2.87%, 28.80% ± 3.62% and 29.25% ± 2.65% at days 5, 10, and 3 after the cessation of OA-4 treatment, respectively. It’s worth noting that OA-4 is superior to lamivudine in the inhibition of rebound of viral replication rate. The structure–activity relationships of OA derivatives had been preliminary discussed, which should be useful to explore further novel anti-HBV agents. View Full-Text
Keywords: oleanolic-acid derivatives; epoxy ring; eosin Y; anti-hepatitis B virus; virus recrudescence oleanolic-acid derivatives; epoxy ring; eosin Y; anti-hepatitis B virus; virus recrudescence
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).

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

Yan, W.; Zhang, C.; Li, B.; Xu, X.; Liang, M.; Gu, S.; Chu, F.; Xu, B.; Ren, J.; Wang, P.; Lei, H. A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation. Molecules 2016, 21, 402.

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]

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