40662-29-1Relevant articles and documents
Mechanistic Studies of the Photoinduced Quinone Trimethyl Lock Decaging Process
Regan, Clinton J.,Walton, David P.,Shafaat, Oliver S.,Dougherty, Dennis A.
, p. 4729 - 4736 (2017)
Mechanistic studies of a general reaction that decages a wide range of substrates on exposure to visible light are described. The reaction involves a photochemically initiated reduction of a quinone mediated by an appended thioether. After reduction, a trimethyl lock system incorporated into the quinone leads to thermal decaging. The reaction could be viewed as an electron-transfer initiated reduction of the quinone or as a hydrogen abstraction-Norrish Type II-reaction. Product analysis, kinetic isotope effects, stereochemical labeling, radical clock, and transient absorption studies support the electron transfer mechanism. The differing reactivities of the singlet and triplet states are determined, and the ways in which this process deviates from typical quinone photochemistry are discussed. The mechanism suggests strategies for extending the reaction to longer wavelengths that would be of interest for applications in chemical biology and in a therapeutic setting.
Natural product-inspired profluorophores for imaging NQO1 activity in tumour tissues
Cheng, Zhiming,Valen?a, Wagner O.,Dias, Gleiston G.,Scott,Barth, Nicole D.,de Moliner,Souza, Gabriela B.P.,Mellanby, Richard J.,Vendrell, Marc,da Silva Júnior, Eufranio N.
, p. 3938 - 3946 (2019)
Herein we designed a collection of trimethyl-lock quinone profluorophores as activity-based probes for imaging NAD(P)H:quinone oxidoreductase (NQO1) in cancer cells and tumour tissues. Profluorophores were prepared via synthetic routes from naturally-occu
Synthesis of bioreductive esters from fungal compounds
Weerapreeyakul, Natthida,Anorach, Rutchayaporn,Khuansawad, Thidarut,Yenjai, Chavi,Isaka, Masahiko
, p. 930 - 935 (2007)
Four new bioreductive esters (7-10) have been synthesized. Their structures composed of trimethyl lock containing quinone propionic acid with an ester linkage to the fungal cytotoxic compounds; preussomerin G (1), preussomerin I (2), phaseolinone (3) and phomenone (4). The synthesized esters are aimed to act via reductive activation specifically at the cancer cells, resulting from hypoxia and overexpression of reductases. Hence, the toxicity will be lessened during distribution across the normal cells. The anticancer activity was determined in cancer cell lines with reported reductase i.e., BC-1 cells and NCI-H187 as well as in non-reductase containing cancer cells; KB cells. When considering each cell lines, result showed that structure modification giving to 7-10 led to less cytotoxicity than their parent compounds (1-4). Both 7 and 8 were strongly cytotoxic (IC50≤5 μg/ml) to NCI-H187, whereas 9 and 10 were moderately cytotoxic (IC50=6-10 μg/ml) to BC-1 cells. Additional study of stability of represented phenolic ester (8) and an alcoholic ester (9) were performed. Result illustrated that both 8 and 9 were stable in the presence of esterase. Therefore, the cytotoxicity of the synthesized compounds (8-10) might be due to partial bioreductive activation in the cancer cells.
HNQO1-ACTIVATABLE FLUORESCENT PROBE FOR IMAGING CANCER CELLS IN-VITRO AND IN-VIVO
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Paragraph 0088-0090; 0092, (2021/05/28)
The present invention includes a probe, an assay, a method of detecting, a human NAD(P)H quinone oxidoreductase-1 (hNQO1) enzyme activity with a fluorescent probe comprising a quinone propionic acid (QPA) conjugated to dicyanoisophorone (DCP), wherein the
Pyroptosis drug prodrug, preparation method thereof and pyroptosis drug
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Paragraph 0125; 0128; 0130, (2021/06/13)
The invention discloses a pyroptosis drug prodrug, a preparation method thereof and a pyroptosis drug. The pyroptosis drug prodrug provided by the invention can cause mitochondria damage, release cytochrome c and activate Caspase3 to shear GSDME by targeting mitochondria, so that pyroptosis of cells occurs. The prodrug (NCyNH2) has selectivity to tumor cells, damage to normal cells is reduced, and the activation condition of the prodrug (NCyNH2) can be detected through recovery of self-fluorescence. After intratumor administration, the prodrug can effectively regulate the tumor immune microenvironment and activate T cell mediated anti-tumor immune response. The molecule has huge application prospects in the aspects of mitochondrial targeting, cell respiration inhibition, pyroptosis induction, tumor immune microenvironment improvement, T cell mediated anti-tumor immune response activation and the like.
NQO1-selective activated prodrugs of combretastatin A-4: Synthesis and biological evaluation
Li, Manping,Li, Sen,Li, Yue,Ma, Xin,Qu, Yan,Wu, Liqiang,Zhang, Chong
, (2020/09/04)
Tumor-specific prodrug treatment renders the exclusive delivery of antitumor agents with the lowest untoward effects. In this work, we reported the synthesis and biological assessment of four NQO1-activatable combretastatin A-4 prodrugs constituted by active drug CA-4, different self-immolating linkers, and NQO1-responsive trigger groups. The in vitro antiproliferative activities showed that prodrug 4 displayed greater selective toxicity toward the tumor cells that overexpressed NQO1, taxol-resistant A549 cells, hypoxia-exposed A549 and HepG2 cells, and incurred lower damage to normal cells in comparison with combretastatin A-4, prodrugs 1, 2, and 3. Moreover, based on a mechanistic study, NQO1 triggered prodrug 4 to effectively liberate the parent drug combretastatin A-4 and kill tumor cells. Furthermore, we also demonstrated that prodrug 4 exerted a stronger anticancer effect and greater safety than combretastatin A-4 under in vivo conditions. Hence, from the above results, NQO1 can be used as a specific delivery system for releasing anticancer agents; besides, prodrug 4 can serve as a candidate lead for developing specific anticancer agents.
