2. Academic Validation
  3. Synthesis of novel tylophorine derivatives and evaluation of their anti-inflammatory activity

Synthesis of novel tylophorine derivatives and evaluation of their anti-inflammatory activity

  • ACS Med Chem Lett. 2014 Jul 23;5(9):1027-31. doi: 10.1021/ml500255j.
Ti Wen 1,  Ziwen Wang 2,  Xianyi Meng 3,  Meng Wu 4,  Yangguang Li 3,  Xiaoli Wu 3,  Liqing Zhao 3,  Puyue Wang 3,  Zhinan Yin 3,  Jesse Li-Ling 5,  Qingmin Wang 4
Affiliations

Affiliations

  • 1 Department of Medical Oncology, First Hospital of China Medical University , Shengyang 110001, China.
  • 2 State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, China ; Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education, College of Chemistry, Tianjin Normal University , Tianjin 300387, China.
  • 3 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300071, China.
  • 4 State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University , Tianjin 300071, China.
  • 5 Joint Key Laboratory for Bio-Resource Research and Utilization of Sichuan and Chongqing, Institute of Medical Genetics, School of Life Science, Sichuan University , Chengdu 610041, China.
PMID: 25221661 DOI: 10.1021/ml500255j
Abstract

We have previously demonstrated that DCB-3503, a tylophorine analogue, has an anti-inflammatory property in murine models for autoimmune diseases. However, its mechanism remains unknown. Here, we have synthesized 34 derivatives of DCB-3503 and investigated their effects on T cells differentiation and TNF-α production. Six derivatives (4, 9, 13, 19, 31, and 32) could significantly promote the expression of Foxp3. Among these, the IC50 of 31 and 32 was about 500 μM. Eight analogues (1, 2, 4, 9, 12, 18, 19, and 21) showed anti-TNF-α effect in Raw 264.7 cells and murine splenocytes, of which 18 and 19 were most significant. Moreover, 31 and 18 showed a better activity and cell survival ratio when compared with DCB-3503 at various concentrations. In summary, we have demonstrated the anti-inflammatory characteristics of 34 novel tylophorine derivatives and discussed their structure-activity relationship in order to explore their therapeutic potentials for inflammatory diseases.

Keywords

Foxp3; TNF-α; Tylophorines derivatives; anti-inflammatory activity.

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