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.
References
Aug 1, 1986·Journal of Medicinal Chemistry·I A ShaikhA P Grollman
Sep 5, 2002·International Journal of Cancer. Journal International Du Cancer·Maria FribergScott J Antonia
Jun 10, 2004·Bioorganic & Medicinal Chemistry·Jin Sung KimChong-Ock Lee
Oct 28, 2006·Journal of Natural Products·Alban PereiraRaymond J Andersen
Jan 11, 2007·Archives of Insect Biochemistry and Physiology·Junsuo S LiJianyong Li
Feb 23, 2007·Archiv der Pharmazie·Andrea DefantInes Mancini
Feb 26, 2008·Bioorganic & Medicinal Chemistry·Yu ChengLian-Quan Gu
Mar 6, 2008·Journal of Medicinal Chemistry·Sanjeev KumarAlexander J Muller
Nov 22, 2008·Biochemical Society Transactions·Sarah J ThackrayStephen K Chapman
Jan 29, 2009·Archiv der Pharmazie·Andrea DefantInes Mancini
Jun 11, 2009·Journal of Medicinal Chemistry·Eddy W YueAndrew P Combs
Mar 4, 2010·Blood·Xiangdong LiuPeggy A Scherle
Apr 10, 2014·The Journal of Organic Chemistry·Jinwei SunYun Liu
Dec 6, 2014·Drug Discovery Today·Christopher J D Austin, Louis M Rendina
May 15, 2015·Journal of Medicinal Chemistry·Ute F RöhrigOlivier Michielin
Jul 21, 2015·European Journal of Medicinal Chemistry·Le-Mao YuLin-Kun An
Mar 23, 2017·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Lieve BrochezVibeke Kruse
Dec 9, 2017·European Journal of Medicinal Chemistry·Tianwei WengJinlei Bian
Dec 17, 2017·Cancer Research·George C PrendergastAlexander J Muller
May 16, 2017·MedChemComm·Alice ColettiAntonio Macchiarulo
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
Jun 12, 2021·Organic & Biomolecular Chemistry·Sunmi KimIkyon Kim
Jul 31, 2021·Bioorganic Chemistry·Halil I CiftciAmaç Fatih Tuyun
Nov 21, 2020·Journal of Medicinal Chemistry·Xi FengJinlei Bian