2. Academic Validation
  3. Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase

Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase

  • Bioorg Med Chem Lett. 2020 Jun 1;30(11):127159. doi: 10.1016/j.bmcl.2020.127159.
Yuanyuan Li 1,  Shengnan Zhang 2,  Rong Wang 3,  Menghan Cui 4,  Wei Liu 5,  Qing Yang 6,  Chunxiang Kuang 7
Affiliations

Affiliations

  • 1 Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, 200092 Shanghai, China. Electronic address: [email protected].
  • 2 State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, 2005 Songhu Road, 200438 Shanghai, China. Electronic address: [email protected].
  • 3 Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, 200092 Shanghai, China. Electronic address: [email protected].
  • 4 Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, 200092 Shanghai, China. Electronic address: [email protected].
  • 5 School of Pharmacy, Nantong University, 19 Qixiu Road, 226001 Nantong, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, 2005 Songhu Road, 200438 Shanghai, China. Electronic address: [email protected].
  • 7 Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, 200092 Shanghai, China. Electronic address: [email protected].
PMID: 32247733 DOI: 10.1016/j.bmcl.2020.127159
Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as Cancer and neurodegenerative diseases. The search for IDO1 Inhibitor has been intensely pursued but there is a paucity of potent TDO and IDO1/TDO dual inhibitors. Natural product tryptanthrin has been confirmed to bear IDO1 and/or TDO inhibitory activities. Herein, twelve novel tryptanthrin derivatives were synthesized and evaluated for the IDO1 and TDO inhibitory potency. All of the compounds were found to be IDO1/TDO dual inhibitors, in particular, compound 9a and 9b bore IDO1 inhibitory activity similar to that of INCB024360, and compound 5a and 9b had remarkable TDO inhibitory activity superior to that of the well-known TDO inhibitor LM10. This work enriches the collection of IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs.

Keywords

IDO1 inhibitor; IDO1/TDO dual inhibitor; Novel tryptanthrin derivative; TDO inhibitor; Water solubility.

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