Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 169, Issue -, Pages 29-41Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.02.063
Keywords
Platinum(IV) complexes; Tryptophan-2,3-dioxygenase; Immunomodulator; Anticancer; Chemo-immunotherapy
Categories
Funding
- National Natural Science Foundation of China [21571033, 81503099]
- Jiangsu Province Natural Science Foundation [BK20150643]
- Fundamental Research Funds for the Central Universities [2242017K41024]
- Jiangsu KeyGen Biotech Company
Ask authors/readers for more resources
Increasing evidences suggested that cisplatin can be involved in a tumor-specific immune response as an immunomodulator to improve antitumor immunity, but the designation and development are limited. Here, we report a series of novel Pt(IV) complexes derived from the conjugation of platinum(II) anticancer agents with an immune checkpoint TDO inhibitor. These complexes not only showed significant cytotoxic effects on the tested cancer cell lines, but also could enhance antitumor immune response. Particularly, complex 72, the mono-conjuagte of oxoplatin and (E)-4-oxo-4-(3-(2-(pyridin-3-yl)vinyl)-1H-indol-1-yl)butanoic acid, displayed 35-fold more potency than cisplatin against TDO-overexpressed HepG-2 cancer cells. Further study indicated that 12 could inhibit TDO via releasing a derivative of a TDO inhibitor and block kynurenine production, resulting in 1-cell activation and proliferation in vitro. In vivo tests proved that T2 as a potent immunomodulator could highly promote the antitumor activity of cisplatin and effectively suppress the expression of TDO. This immunochemotherapeutic strategy can be promisingly applied to treat with TDO-overexpressed cancers. (C) 2019 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available