2. Academic Validation
  3. Discovery and biological evaluation of a new type of dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase from ethnomedicinal plant Dactylicapnos scandens

Discovery and biological evaluation of a new type of dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase from ethnomedicinal plant Dactylicapnos scandens

  • Phytochemistry. 2023 Jul 25;214:113794. doi: 10.1016/j.phytochem.2023.113794.
Mei-Fen Bao 1,  Xin-Ni Yang 1,  Jing Wu 2,  Jiang-Xin Liu 3,  Xiang-Hai Cai 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: [email protected].
  • 4 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: [email protected].
PMID: 37499850 DOI: 10.1016/j.phytochem.2023.113794
Abstract

The root of Dactylicapnos scandens (D.Don.) Hutch (Papaveraceae), one of the most famous ethno-medicinal Plants from the Bai communities in P. R. China, is used to treat various inflammations and tumours. Bioassay-guided phytochemical research on D. scandens followed by semi-synthesis led to a series of undescribed tetrahydroisoquinoline Alkaloids with dual inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). The previously undescribed dark-green alkaloid dactycapnine A exhibited the best dual inhibitor effects among the identified compounds. Structure-activity relationship analysis revealed the importance of the base skeleton with a hyperconjugation system. The performed semi-synthesis further yielded bioactive dimeric and trimeric compounds with hyperconjugated systems. Performed STD NMR experiments disclosed direct interactions between dactycapnine A and IDO1/TDO. Inhibition kinetics indicated dactycapnine A as a mixed-type dual inhibitor. These findings provided a possible explanation for the Anticancer properties of the ethno-medicinal plant species D. scandens.

Keywords

Aporphine-type alkaloids; Dactycapnine a; Dactylicapnos scandens (D. don) hutch.; IDO1/TDO dual inhibitor; Isoquinoline alkaloids.

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