Synthesis and evaluation of a novel series of quinoline derivatives with immunosuppressive activity.
A series of quinoline derivatives were synthesized and their immunosuppressive activity and cytotoxicity were evaluated with a T-cell functional assay and MTT method, respectively. Most of 5,7-dimethoxyquinolin-4-yl ortho-substituted benzoate derivatives (18, 22, 24, 28, 31 and 37) showed a quite stronger inhibitory activity compared to other analogs. Among the synthesized compounds, 5,7-dimethoxyquinolin-4-yl 2,6-dichlorobenzoate (22) and 5,7-dimethoxyquinolin-4-yl 4-methylbenzenesulfonate (40) exhibited a potent inhibitory activity without significant cytotoxicity at 10 microM concentration. The preliminary mechanism of the active compounds 22 and 40 was further clarified based on the fluorescence activated cell sorter (FACS) assay, and the compounds exerted immunosuppressive activity via inhibiting the T cell activation in a dose dependent manner.
Liu
Guo-Biao
GB
Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
Xu
Jian-Liang
JL
He
Cui-Cui
CC
Chen
Gong
G
Xu
Qiang
Q
Xu
Hong-Xi
HX
Li
Jian-Xin
JX
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D007166:Immunosuppressive Agents; D011804:Quinolines