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MedChemComm
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DOI: 10.1039/C6MD00344C
ARTICLE
Journal Name
56, 178, 350, 422, 750 and 1000 mg/kg administered Notes and references
intraperitoneally (i.p.). Every dose was given 6 mice, compound 1f
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showed the safe dose range of 1f.
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(
Statement: All experiments were performed in compliance with
3
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the relevant laws and institutional guidelines, and the institutional
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Table 3 Acute toxicity test of compound 1f
Dose
(mg/kg)
Mice Number
Start/End
Death rate
(%)
LD50
(mg/kg)
95%CIs
6
7
1000
750
422
350
178
56
6/6
6/6
6/4
6/3
6/0
6/0
100
100
67
50
0
362.46
233.83-561.85
8
9
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Conclusion
A new method to synthesize peroxo bridge was established by using
Eosin Y as photosensitive catalytic oxidizer. Comparedwith the
conventional synthetic methods, it was in lower consumption and
more convenient. Therefore, our synthesis of peroxide bridges had
been optimized by the special catalyzer. A series of novel steroid
derivatives containing peroxide bridge were synthesized using this
method, and their bioactivity tests showed that most derivatives
had anti-HBV activities. In particularly, compound 1f exhibited
higher inhibitory against HBsAg and HBeAg secretion in HepG2.2.15
cells, while nearly no cytotoxicity on HepG2.2.15 cells at 3.13 µg/mL,
showing good therapeutic index.
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The structures were significantly different between steroid
derivatives and 3TC. Although, lamivudine was no longer
recommended as first-line therapy for chronic hepatitis B, and using
lamivudine judiciously on the clinical and scientific research was
paramount 22. Unlike the metabolism antagonism of 3TC, steroids
might indicate yet another mechanism that is related with the
capacity of steroid hormones to intercalate into cell membrane
bilayer and alter membrane fluidity 23. This property of the steroids
would affect the insertion of viral glycoproteins further inhibiting
23 K. P. Whiting, C. J. Restall and P. F. Brain, Life sciences, 2000, 67,
743-757.
4
the assembly of virus particles , which was pending further study.
Therefore, these compounds were expected in collaboration with
3TC for the treatment of hepatitis B diseases. In summary, the
steroid derivatives with peroxide bridges demonstrated potential
anti-HBV activity, and it provided us new ideas to discover anti-HBV
leading compounds.
Acknowledgments
This study was financially supported by the National Natural Science
Foundation of China (No. 81173519) and the Innovation Team
Project Foundation of Beijing University of Chinese Medicine (Lead
Compound Discovering and Developing Innovation Team Project
Foundation).
4 | J. Name., 2012, 00, 1-3
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