Abstract |
A beta-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)- beta-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38muM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89microM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77microM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle.
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Authors | Yun-Hua Wang, Jian-Guo Tang, Rui-Rui Wang, Liu-Meng Yang, Ze-Jun Dong, Li Du, Xu Shen, Ji-Kai Liu, Yong-Tang Zheng |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 355
Issue 4
Pg. 1091-5
(Apr 20 2007)
ISSN: 0006-291X [Print] United States |
PMID | 17336271
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- Carbolines
- Furans
- flazinamide
- HIV Integrase
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Topics |
- Anti-HIV Agents
(chemistry, pharmacology, toxicity)
- Carbolines
(chemistry, pharmacology, toxicity)
- Cell Line
- Cell Survival
(drug effects)
- Furans
(chemistry, pharmacology, toxicity)
- HIV Integrase
(metabolism)
- HIV-1
(drug effects, physiology)
- Molecular Structure
- Protein Binding
- Virus Replication
(drug effects)
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