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Title: Flazinamide, a novel {beta}-carboline compound with anti-HIV actions

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 0.38 {mu}M, 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 0.89 {mu}M, 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 0.77 {mu}M, 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.

Authors:
 [1];  [2];  [3];  [2];  [1];  [2];  [1];  [3];  [4];  [2];  [4];  [3];  [5]
  1. Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China)
  2. (China)
  3. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650204 (China)
  4. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203 (China)
  5. Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China). E-mail: zhengyt@mail.kiz.ac.cn
Publication Date:
OSTI Identifier:
20979891
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.02.081; PII: S0006-291X(07)00379-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; ANTIGENS; BIOSYNTHESIS; LIFE CYCLE; TOXICITY

Citation Formats

Wang Yunhua, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Tang Jianguo, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Wang Ruirui, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Yang Liumeng, Dong Zejun, Du Li, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Shen Xu, Liu Jikai, and Zheng Yongtang. Flazinamide, a novel {beta}-carboline compound with anti-HIV actions. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.02.081.
Wang Yunhua, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Tang Jianguo, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Wang Ruirui, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Yang Liumeng, Dong Zejun, Du Li, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Shen Xu, Liu Jikai, & Zheng Yongtang. Flazinamide, a novel {beta}-carboline compound with anti-HIV actions. United States. doi:10.1016/j.bbrc.2007.02.081.
Wang Yunhua, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Tang Jianguo, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Wang Ruirui, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Yang Liumeng, Dong Zejun, Du Li, Graduate School of the Chinese Academy of Sciences, Beijing 100039, Shen Xu, Liu Jikai, and Zheng Yongtang. Fri . "Flazinamide, a novel {beta}-carboline compound with anti-HIV actions". United States. doi:10.1016/j.bbrc.2007.02.081.
@article{osti_20979891,
title = {Flazinamide, a novel {beta}-carboline compound with anti-HIV actions},
author = {Wang Yunhua and Graduate School of the Chinese Academy of Sciences, Beijing 100039 and Tang Jianguo and Graduate School of the Chinese Academy of Sciences, Beijing 100039 and Wang Ruirui and Graduate School of the Chinese Academy of Sciences, Beijing 100039 and Yang Liumeng and Dong Zejun and Du Li and Graduate School of the Chinese Academy of Sciences, Beijing 100039 and Shen Xu and Liu Jikai and Zheng Yongtang},
abstractNote = {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 0.38 {mu}M, 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 0.89 {mu}M, 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 0.77 {mu}M, 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.},
doi = {10.1016/j.bbrc.2007.02.081},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 355,
place = {United States},
year = {Fri Apr 20 00:00:00 EDT 2007},
month = {Fri Apr 20 00:00:00 EDT 2007}
}