Anti Human Immunodeficiency Virus Type 1 (HIV-1) Agents 4. Discovery of 5,5 '-(p-Phenylenebisazo)-8-hydroxyquinoline Sulfonates as New HIV-1 Inhibitors in Vitro

To search for compounds with superior anti-human immunodeficiency virus type 1 (HIV-1) activity, ten 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline sulfonates (4a-j) were synthesized and preliminarily evaluated as HIV-1 inhibitors in vitro for the first time. Some compounds demonstrated anti-HIV-1 activity, especially 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline p-ethylbenzenesulfonate (4g) and 5,5'-(p-phenylenebisazo)-8-hydroxyquinoline p-chlorobenzenesulfonate (41) showed the more potent anti-HIV-1 activity with 50% effective concentration (EC50) values of 2.59 and 4.01 mu g/ml, and therapeutic index (TI) values of 31.77 and 24.51, respectively.

We thank Wei Chen, Jian Bai, and Feng Cheng of Beijing Institute of Genomics for their contribution in genotyping and data processing and three anonymous reviewers for their critical and constructive comments. We also thank the people of Shangri-La and De Qin Xians, Yunnan Province; Mag Xiang and Zhaxizong Xiang, Tibet Autonomous Region, for their cooperation and hospitality during data collection. We are grateful to the Tibet Academy of Social Sciences for their collaboration and enabling permission to collect data in Mag Xiang. This work was supported by the National Science Foundation; National Institutes of Health National Center for Research Resources, National Institute of General Medical Sciences, National Cancer Institute, National Heart, Lung, and Blood Institute; National Natural Science Foundation of China Grant 30890031 and Ministry of Science and Technology Grant 2006DFA31850 (to C.Z.); Chinese Academy of Sciences Grant KSCX2-YW-R-76 and Science and Technology Plan of the Tibet Autonomous Region Grant 2007-2-18 to Beijing Genomics Institute at Shenzhen; and an International Joint Project award from the Royal Society. This consortium grew from a catalysis meeting sponsored by the National Science Foundation-supported National Evolutionary Synthesis Center (http://www.NESCent.org).