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.
Rational designed highly sensitive NQO1-activated near-infrared fluorescent probe combined with NQO1 substrates in vivo: An innovative strategy for NQO1-overexpressing cancer theranostics
Gong, Qijie,Yang, Fulai,Hu, Jiabao,Li, Tian,Wang, Pengfei,Li, Xiang,Zhang, Xiaojin
, (2021/07/25)
Since NQO1 is overexpressed in many cancer cells, it can be used as a biomarker for cancer diagnosis and targeted therapy. NQO1 substrates show potent anticancer activity through the redox cycle mediated by NQO1, while the NQO1 probes can monitor NQO1 levels in cancers. High sensitivity of probes is needed for diagnostic imaging in clinic. In this study, based on the analysis of NQO1 catalytic pocket, the naphthoquinone trigger group 13 rationally designed by expanding the aromatic plane of the benzoquinone trigger group 10 shows significantly increased sensitivity to NQO1. The sensitivity of the naphthoquinone trigger group-based probe A was eight times higher than that of benzoquinone trigger group-based probe B in vivo. Probe A was selectively and efficiently sensitive to NQO1 with good safety profile and plasma stability, enabling its combination with NQO1 substrates in vivo for NQO1-overexpressing cancer theranostics for the first time.
Pyroptosis drug prodrug, preparation method thereof and pyroptosis drug
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, (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.
Fluorescent probe molecule for detecting diaphorase based on rhodamine derivative and preparation method and application thereof
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, (2020/07/21)
The invention relates to a fluorescent probe molecule for detecting diaphorase based on a rhodamine derivative and a preparation method and application thereof. The molecular structure of the fluorescent probe is shown in figure 1. The invention also disc
