Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat-TAR interaction inhibitors

Shuguang Chen; Ran Chen; Meizi He; Ruifang Pang; Zhiwu Tan; Ming Yang

doi:10.1016/j.bmc.2009.01.038

Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat-TAR interaction inhibitors

Bioorg Med Chem. 2009 Mar 1;17(5):1948-56. doi: 10.1016/j.bmc.2009.01.038. Epub 2009 Jan 23.

Authors

Shuguang Chen¹, Ran Chen, Meizi He, Ruifang Pang, Zhiwu Tan, Ming Yang

Affiliation

¹ State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.

PMID: 19217787
DOI: 10.1016/j.bmc.2009.01.038

Abstract

Thirty-two quinoline derivatives were designed and synthesized as HIV-1 Tat-TAR interaction inhibitors. All the compounds showed high antiviral activities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Nine of them with low cytotoxicities were evaluated by Tat dependent HIV-1 LTR-driven CAT gene expression colorimetric enzyme assay in human 293T cells, indicating effective inhibitory activities of blocking the Tat-TAR interaction. Molecular modeling experiments indicated that these compounds may inhibit Tat-TAR interaction by binding to Tat protein instead of TAR RNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
Cell Line
Drug Design
HIV Long Terminal Repeat / drug effects*
HIV-1 / drug effects*
Humans
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology*
Structure-Activity Relationship
tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*
tat Gene Products, Human Immunodeficiency Virus / metabolism

Substances

Anti-HIV Agents
Quinolines
tat Gene Products, Human Immunodeficiency Virus