Design, synthesis and structure-activity relationship study of novel naphthoindolizine and indolizinoquinoline-5,12-dione derivatives as IDO1 inhibitors.

Bioorganic & Medicinal Chemistry
Rui YangXiangbao Meng

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as a promising target for cancer immunotherapy. Many naphthoquinone derivatives have been reported as IDO1 inhibitors so far. Herein, two series of naphthoquinone derivatives, naphthoindolizine and indolizinoquinoline-5,12-dione derivatives, were synthesized and evaluated for their IDO1 inhibitory activity. Most of the target compounds showed significant inhibition potency and high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). The structure-activity relationship was also summarized. The most potent compounds 5c (IC50 23 nM, IDO1 enzyme), and 5b' (IC50 372 nM, HeLa cell) were identified as promising lead compounds.

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Citations

Mar 21, 2020·Frontiers in Immunology·Yi-Shu HuangTrevor W Stone
Dec 21, 2020·European Journal of Medicinal Chemistry·Rahul Singh, Deepak B Salunke
Feb 24, 2021·Bioorganic Chemistry·Pratibha Yadav, Kamal Shah
Jul 18, 2020·The Journal of Organic Chemistry·Dirgha Raj JoshiIkyon Kim
Nov 20, 2020·Pharmacology & Therapeutics·Ana DolšakMatej Sova
Apr 28, 2021·Journal of Computer-aided Molecular Design·Huizhen GeXiaojun Yao

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