Design, synthesis, and immunosuppressive activity of new deoxybenzoin derivatives.
In the search for potential immunosuppressive agents with high efficacy and low toxicity, a series of new deoxybenzoins were synthesized and evaluated for their cytotoxicity and immunosuppressive activity. Among the synthesized compounds, four deoxybenzoin oximes (compounds 31, 32, 37, and 38) exhibited lower cytotoxicity and higher inhibitory activity toward anti-CD3/anti-CD28 co-stimulated T-cell proliferation than other compounds. More significantly, compound 31 is >100-fold less cytotoxic than cyclosporine A (CsA) and is also more potent (31: SI>684.64, CsA: SI=235.44). The preliminary inhibition mechanism of compound 31 was also identified by flow cytometry, and this compound exerts immunosuppressive activity by inducing apoptosis in activated lymph node cells in a dose-dependent manner. In addition, the mechanism of apoptosis was detected by western blot analysis.
Li
Huan-Qiu
HQ
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Luo
Yin
Y
Song
Ran
R
Li
Zi-Lin
ZL
Yan
Tao
T
Zhu
Hai-Liang
HL
D000818:Animals; D017209:Apoptosis; D001573:Benzoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D018360:Crystallography, X-Ray; D015195:Drug Design; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008968:Molecular Conformation; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
C552830:2-(4-bromophenyl)-1-(3,4-dihydroxyphenyl)ethanone oxime; D007166:Immunosuppressive Agents; D010091:Oximes; C492807:deoxybenzoin; D001573:Benzoin