191846-77-2Relevant academic research and scientific papers
PYRROLOBENZODIAZEPINE PRODRUGS AND ANTIBODY CONJUGATES THEREOF
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Page/Page column 176; 177, (2018/03/06)
The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.
Design, synthesis, and biological evaluation of NAD(P)H: Quinone oxidoreductase (NQO1)-targeted oridonin prodrugs possessing indolequinone moiety for hypoxia-selective activation
Xu, Shengtao,Yao, Hong,Pei, Lingling,Hu, Mei,Li, Dahong,Qiu, Yangyi,Wang, Guangyu,Wu, Liang,Yao, Hequan,Zhu, Zheying,Xu, Jinyi
, p. 310 - 321 (2017/04/11)
The enzyme NQO1 is a potential target for selective cancer therapy due to its overexpression in certain hypoxic tumors. A series of prodrugs possessing a variety of cytotoxic diterpenoids (oridonin and its analogues) as the leaving groups activated by NQO1 were synthesized by functionalization of 3-(hydroxymethyl)indolequinone, which is a good substrate of NQO1. The target compounds (29a-m) exhibited relatively higher antiproliferative activities against NQO1-rich human colon carcinoma cells (HT-29) and human lung carcinoma (A549) cells (IC50?=?0.263–2.904?μM), while NQO1-defficient lung adenosquamous carcinoma cells (H596) were less sensitive to these compounds, among which, compound 29h exhibited the most potent antiproliferative activity against both A549 and HT-29?cells, with IC50 values of 0.386 and 0.263?μM, respectively. Further HPLC and docking studies demonstrated that 29h is a good substrate of NQO1. Moreover, the investigation of anticancer mechanism showed that the representative compound 29h affected cell cycle and induced NQO1 dependent apoptosis through an oxidative stress triggered mitochondria-related pathway in A549?cells. Besides, the antitumor activity of 29h was also verified in a liver cancer xenograft mouse model. Biological evaluation of these compounds concludes that there is a strong correlation between NQO1 enzyme and induction of cancer cell death. Thus, this suggests that some of the target compounds activated by NQO1 are novel prodrug candidates potential for selective anticancer therapy.
INDQ/NO, a bioreductively activated nitric oxide prodrug
Sharma, Kavita,Iyer, Aishwarya,Sengupta, Kundan,Chakrapani, Harinath
, p. 2636 - 2639 (2013/07/19)
The design, synthesis, and development of INDQ/NO, a novel nitric oxide (NO) prodrug targeted by a bioreductive trigger, are described. INDQ/NO, an indolequinone-diazeniumdiolate is found to be metabolized to produce NO by DT-diaphorase, a bioreductive enzyme that is overexpressed in certain cancers and hypoxic tumors. Cell-based assays revealed that INDQ/NO induces DNA damage and is a potent inhibitor of cancer cell proliferation.
Phosphoramide compounds
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, (2008/06/13)
The invention provides a compound of formula I: wherein R1, Ra, Rb, Rc, and Rd have any of the values defined in the specification, as well as pharmaceutical compositions comprising such compounds or salts. The compounds are useful for treating cancer in animals.
2-cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: Structure-activity in vitro and efficacy in vivo
Naylor, Matthew A.,Jaffar, Mohammed,Nolan, John,Stephens, Miriam A.,Butler, Susan,Patel, Kantilal B.,Everett, Steven A.,Adams, Gerald E.,Stratford, Ian J.
, p. 2335 - 2346 (2007/10/03)
A series of 2-cycloalkyl- and 2-alkyl-3-(hydroxymethyl)-1- methylindoloquinones and corresponding carbamates have been synthesized and substituted in the 5-position with a variety of substituted and unsubstituted aziridines. Cytotoxicity against hypoxic c
