1-Aryl-tetrahydroisoquinoline analogs as active anti-HIV agents in vitro.
A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening revealed that 6,7-dihydroxytetrahydroisoquinolines possessed higher selective index than 6,7-dimethoxyl analogs due to the significantly decreased cytotoxicities. Compounds 6, 24, and 36 showed potent anti-HIV activities with EC(50) values of 8.2, 4.6, and 5.3microM respectively, and the cytotoxicities (CC(50)) of these three compounds were 784.3, 727.3, and 687.3microM, which resulted in SI values larger than 95, 159, and 130 respectively.
Cheng
Pi
P
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, The Chinese Academy of Sciences, Kunming, Yunnan 650204, PR China.
Huang
Ning
N
Jiang
Zhi-Yong
ZY
Zhang
Quan
Q
Zheng
Yong-Tang
YT
Chen
Ji-Jun
JJ
Zhang
Xue-Mei
XM
Ma
Yun-Bao
YB
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D002478:Cells, Cultured; D003500:Cyclization; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000627:therapeutic use*; D018675:Toxicity Tests
D019380:Anti-HIV Agents; D044005:Tetrahydroisoquinolines