59749-85-8Relevant academic research and scientific papers
Non-alkylator anti-glioblastoma agents induced cell cycle G2/M arrest and apoptosis: Design, in silico physicochemical and SAR studies of 2-aminoquinoline-3-carboxamides
Yuan, Pengtao,Gu, Xiangyu,Ni, Xintong,Qi, Yingxue,Shao, Xusheng,Xu, Xiaoyong,Liu, Jianwen,Qian, Xuhong
supporting information, (2021/09/22)
Malignant gliomas are the most common brain tumors, with generally dismal prognosis, early clinical deterioration and high mortality. Recently, 2-aminoquinoline scaffold derivatives have shown pronounced activity in central nervous system disorders. We herein reported a series of 2-aminoquinoline-3-carboxamides as novel non-alkylator anti-glioblastoma agents. The synthesized compounds showed comparable activity to cisplatin against glioblastoma cell line U87 MG in vitro. Among them, we found that 6a displayed good inhibitory activity against A172 and U118 MG glioblastoma cell lines and induced cell cycle arrest in the G2/M phase and apoptosis in U87 MG by flow cytometry analysis. Additionally, 6a displayed low cytotoxicity to several normal human cell lines. In silico study showed 6a had promising physicochemical properties and was predicted to cross the blood–brain barrier. Moreover, preliminary structure–activity relationships are also investigated, shedding light on further modifications towards more potent agents on this series of compounds. Our results suggest this compound has a promising potential as an anti-glioblastoma agent with a differential effect between tumor and non-malignant cells.
Chemical Evolution of Antivirals Against Enterovirus D68 through Protein-Templated Knoevenagel Reactions
Tauber, Carolin,Wamser, Rebekka,Arkona, Christoph,Tügend, Marisa,Abdul Aziz, Umer Bin,Pach, Szymon,Schulz, Robert,Jochmans, Dirk,Wolber, Gerhard,Neyts, Johan,Rademann, J?rg
, p. 13294 - 13301 (2021/05/10)
The generation of bioactive molecules from inactive precursors is a crucial step in the chemical evolution of life, however, mechanistic insights into this aspect of abiogenesis are scarce. Here, we investigate the protein-catalyzed formation of antivirals by the 3C-protease of enterovirus D68. The enzyme induces aldol condensations yielding inhibitors with antiviral activity in cells. Kinetic and thermodynamic analyses reveal that the bioactivity emerges from a dynamic reaction system including inhibitor formation, alkylation of the protein target by the inhibitors, and competitive addition of non-protein nucleophiles to the inhibitors. The most active antivirals are slowly reversible inhibitors with elongated target residence times. The study reveals first examples for the chemical evolution of bio-actives through protein-catalyzed, non-enzymatic C?C couplings. The discovered mechanism works under physiological conditions and might constitute a native process of drug development.
X-ray Structure and Molecular Docking Guided Discovery of Novel Chitinase Inhibitors with a Scaffold of Dipyridopyrimidine-3-carboxamide
Yuan, Pengtao,Jiang, Xi,Wang, Siyu,Shao, Xusheng,Yang, Qing,Qian, Xuhong
, p. 13584 - 13593 (2020/12/02)
Chitinases are the glycosyl hydrolase for catalyzing the degradation of chitin and play an indispensable role in bacterial pathogenesis, fungal cell wall remodeling, and insect molting. Thus, chitinases are attractive targets for therapeutic drugs and pes
Synthesis of new thiazole, bithiazolidinone and pyrano [2,3-d] thiazole derivatives as potential antimicrobial agents
Salem, Mohamed A.
, p. 1 - 9 (2017/05/29)
In an attempt to find a new class of antimicrobial agents, a series of thiazole derivatives containing furan moiety 3, 7, 8a,b, 10a-c and 12 were prepared via the reaction of 2-cyano-N-(furan-2-ylmethyl)acetamide (1) with phenyl isothiocyanate and α-halocarbonyl compounds. Also, many bithiazolidinone and pyranothiazole derivatives were synthesized through interaction of thiazolidinone 7 with appropriate electrophilic reagents. These compounds were screened for their antibacterial and antifungal activity. Among the synthesized compounds, thiazole derivatives 23a and 23b were equipotent to gentamycin against K. pneumonia (MIC 0.49 μg/mL), and showed in vitro antifungal activity equipotent to amphotericin B versus A. fumigatus (MIC 0.98 μg/mL), A. clavatus (MIC 0.98 μg/mL) and G. candidium (MIC 0.49 μg/mL). Also, bithiazolidinones 14 and 15 were equipotent to amphotericin B in inhibiting the growth of A. clavatus (MIC 0.98 μg/mL) and G. candidium (MIC 0.49 μg/mL). Structures of the newly synthesized compounds were established by elemental analysis and spectral data.
Discovery and structure-activity relationships of small molecules that block the human immunoglobulin G-human neonatal Fc receptor (hIgG-hFcRn) protein-protein interaction
Wang, Zhaolin,Fraley, Cara,Mezo, Adam R.
, p. 1253 - 1256 (2013/03/14)
The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease. Small molecules that block the protein-protein interactions of human IgG-human FcRn may lower pathogenic autoantibodies and provide effective treatment. A novel class of quinoxalines has been discovered as antagonists of the IgG:FcRn protein-protein interaction through optimization of a hit derived from a virtual ligand-based screen.
2-cyano-2-alkoximino-acetamides
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, (2008/06/13)
Novel fungicides of the formula STR1 in which R1 represents optionally substituted hydroxyalkyl, optionally substituted hydroxyalkoxyalkyl, optionally substituted heteroarylalkyl or optionally substituted heteroaryl, and R2 represents optionally substituted alkyl, optionally substituted alkenyl, or alkinyl. Intermediate therefor, wherein R2 is hydrogen or an alkali metal cation, are also new.
