3240-94-6Relevant academic research and scientific papers
A Cofactor-Substrate-Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions
Duan, Chunying,Gao, Xu,Jiao, Yang,Si, Wen,Zhang, Lei
, p. 6021 - 6027 (2020)
Identifying the location and expression levels of enzymes under hypoxic conditions in cancer cells is vital in early-stage cancer diagnosis and monitoring. By encapsulating a fluorescent substrate, L-NO2, within the NADH mimic-containing metal–organic capsule Zn-MPB, we developed a cofactor-substrate-based supramolecular luminescent probe for ultrafast detection of hypoxia-related enzymes in solution in vitro and in vivo. The host–guest structure fuses the coenzyme and substrate into one supramolecular probe to avoid control by NADH, switching the catalytic process of nitroreductase from a double-substrate mechanism to a single-substrate one. This probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra-molecular pathway with increased activity. The enzyme content and fluorescence intensity showed a linear relationship and equilibrium was obtained in seconds, showing potential for early tumor diagnosis, biomimetic catalysis, and prodrug activation.
PIM KINASE INHIBITOR COMPOSITIONS AND USES THEREOF
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Paragraph 0240, (2020/11/12)
This disclosure relates to compounds and compositions useful as inhibitors of PIM kinases. Also provided are methods of synthesis and methods of use of PIM inhibitors in treating individuals suffering from cancerous malignancies.
In silico/in vitro screening and hit evaluation identified new phenothiazine anti-prion derivatives
Bolognesi, Maria Laura,Carloni, Paolo,Colini Baldeschi, Arianna,Gandini, Annachiara,Legname, Giuseppe,Rossetti, Giulia,Salzano, Giulia,Tran, Thanh Hoa,Zaccagnini, Ludovica
supporting information, (2020/04/21)
Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of rare neurodegenerative disorders. TSEs are characterized by the accumulation of prions (PrPSc) that represent pathological isoforms of the physiological cellular prion protein PrPC. Although the conversion of PrPC to PrPSc is still not completely understood, blocking this process may lead to develop new therapies. Here, we have generated a pharmacophore model, based on anti-prion molecules reported in literature to be effective in phenotypic assay. The model was used to conduct a virtual screen of commercial compound databases that selected a small library of ten compounds. These molecules were then screened in mouse neuroblastoma cell line chronically infected with prions (ScN2a) after excluding neurotoxicity. 1 has been identified as the therapeutic hit on the basis of the following evidence: chronic treatments of ScN2a cells using 1 eliminate PrPSc loaded in both Western blotting analysis and Real-Time Quaking-Induced Conversion (RT-QuIC) assay. We also proposed the mechanism of action of 1 by which it has the ability to bind PrPC and consequentially blocks prion conversion. Herein we describe the results of these efforts.
C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS
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Page/Page column 47, (2018/03/06)
The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
C-3 NOVEL TRITERPENE WITH C-17 AMINE DERIVATIVES AS HIV INHIBITORS
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Page/Page column 25; 26, (2017/09/15)
The present invention relates to to C-3 novel triterpene with C-17 amine derivatives of formula (I); or pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5 and 'n' are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) and process for preparing them, and their use for the treatment of viral diseases and particularly HIV mediated diseases.
Highly Water-Soluble Cyclopentadienyl and Indenyl Molybdenum(II) Complexes - Second Generation of Molybdenum-Based Cytotoxic Agents
Mr?zek, Ond?ej,?ebestová, Lucie,Vinklárek, Jaromír,?ezá?ová, Martina,Eisner, Ale?,R??i?ková, Zdeňka,Honzí?ek, Jan
, p. 519 - 529 (2016/02/16)
A series of the cyclopentadienyl and indenyl molybdenum compounds bearing alkylammonium functions [(η5-Cp′)Mo(CO)2(N,NL)][BF4]2 were synthesized and characterized by analytical and spectroscopic methods. The structures of [{η5-C5H4CH2CH2NH(CH2)5}Mo(CO)2(4,7-Ph2-phen)][BF4]2 (4,7-Ph2-phen = 4,7-diphenyl-1,10-phenanthroline) and [(η5-C9H6CH2CH2NHMe2)Mo(CO)2(phen)][BF4]2 (phen = 1,10-phenanthroline) were determined by X-ray crystallography. All of the synthesized compounds exhibit high activity against the human leukemia cell lines MOLT-4 and HL-60. They are approximately one order of magnitude more active than cisplatin. This study has proven that the modification of the outer coordination sphere of molybdenum complexes has a strong impact on their activity and may be successfully used for the design of new highly cytotoxic active species. A series of highly cytotoxic molybdenum(II) complexes are synthesized, and their activity against MOLT-4 and HL-60 leukemia cells is established.
A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
, p. 420 - 430 (2015/12/31)
α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism in Vivo
Dong, Ze-Xi,Shi, Zhi-Hao,Li, Nian-Guang,Zhang, Wei,Gu, Ting,Zhang, Peng-Xuan,Wu, Wen-Yu,Tang, Yu-Ping,Fang, Fang,Xue, Xin,Li, He-Min,Cheng, Hai-Bo,Yang, Jian-Ping,Duan, Jin-Ao
, p. 946 - 957 (2016/05/24)
Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2O2-induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment. Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. The results of the biological evaluation showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.
HETEROCYCLE SUBSTITUTED AMINO-PYRIDINE COMPOUNDS AND METHODS OF USE THEREOF
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Paragraph 0362; 0364, (2016/04/20)
The present disclosure relates to heterocycle substituted amino-pyridine compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
Synthesis of scutellarein derivatives to increase biological activity and water solubility
Shi, Zhi-Hao,Li, Nian-Guang,Shi, Qian-Ping,Zhang, Wei,Dong, Ze-Xi,Tang, Yu-Ping,Zhang, Peng-Xuan,Gu, Ting,Wu, Wen-Yu,Fang, Fang,Xin-Xue,Li, He-Min,Yang, Jian-Ping,Duan, Jin-Ao
, p. 6875 - 6884 (2015/11/11)
In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease.
