title: Design, synthesis, and biological evaluation of chalcone oxime derivatives as potential immunosuppressive agents.
abstract: A series of deoxybenzoin oximes were recently reported as potent immunosuppressive agents by our group. In order to continue the original research for potential immunosuppressive agents with high efficacy and low toxicity, we synthesized a series of new chalcone oximes and evaluated them for their cytotoxicities and immunosuppressive activities. Among the synthesized compounds, chalcone oximes 25 and 27 exhibited lower cytotoxicities and higher inhibitory activities on anti-CD3/anti-CD28 co-stimulated lymph node cells than other compounds. Specially, compound 27 displayed 200-fold lower cytotoxicity (CC(50)=2174.39 μM) than cyclosporin A (CC(50)=10.10 μM) and showed SI value (SI=176.69) close to cyclosporin A (SI=154.13). Besides, the preliminary mechanism of inhibition effect of compounds 25 and 27 was also detected by flow cytometry, and the compounds exerted immunosuppressive activities via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Also, the deep mechanism of apoptosis was detected by Western blot analysis.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Luo
authors.forename: Ran
authors.initials: R
authors.lastname: Song
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D007166:Immunosuppressive Agents; D010091:Oximes; D016572:Cyclosporine