Synthesis of analogues of flazin, in particular, flazinamide, as promising anti-HIV agents.
Flazin isolated from the fruiting bodies of Suillus granulatus was found to possess weak anti-HIV activity (EC(50)=2.36 microM, TI=12.1). To establish a SAR study, 46 flazin analogues were synthesized, and their anti-HIV activities were evaluated in vitro. Among them, flazinamide (9a) showed the most potent activity with an EC(50) value of 0.38 microM and a TI value of 312.0. The results suggested that appropriate substituents at positions 3, 1', and 5' of flazin might play a crucial role in determining their anti-HIV activities, and that flazinamide can be considered as a promising, readily available anti-HIV agent.
Tang
Jian-Guo
JG
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, P.R. China.
Wang
Yun-Hua
YH
Wang
Rui-Rui
RR
Dong
Ze-Jun
ZJ
Yang
Liu-Meng
LM
Zheng
Yong-Tang
YT
Liu
Ji-Kai
JK
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D002243:Carbolines; D005663:Furans; C518828:flazinamide; C055780:flazin