- A Set of Highly Sensitive Sirtuin Fluorescence Probes for Screening Small-Molecular Sirtuin Defatty-Acylase Inhibitors
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Human sirtuins (SIRT1-7) regulate not only deacetylation but also deacylation of fatty acid-derived acyl moieties (defatty-acylation) at the ?-amino group of lysine residues. SIRT-subtype-specific defatty-acylase activity modulators are needed for detailed investigation of the biological roles of these enzymes, and to find suitable small molecules, we require appropriate screening systems. Here, we designed and synthesized a set of SIRT defatty-acylase activity probes with various quencher moieties and peptide sequences based on our previously developed one-step FRET-based SIRT probe SFP3, using improved methodology. Scanning of this set of probes with SIRT isozymes revealed that certain probe/isozyme combinations showed especially high responses. To illustrate the utility of the combinations thus identified, we applied compound 18/SIRT2 for inhibitor screening of a large chemical library. This enabled us to discover a new small molecule SIRT2-specific defatty-acylase inhibitor.
- Nakajima, Yuya,Kawaguchi, Mitsuyasu,Ieda, Naoya,Nakagawa, Hidehiko
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supporting information
p. 617 - 624
(2021/04/07)
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- Design, synthesis and preliminary bioactivity evaluations of 8-hydroxyquinoline derivatives as matrix metalloproteinase (MMP) inhibitors
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Matrix metalloproteinases (MMPs) play important roles in many diseases including cancer. With moderate metal-binding affinity, 8-hydroxyquinoline has gained much interest in current drug design and development. Specially, it has been reported that 8-hydroxyquinoline derivatives serve as MMP-2 inhibitors with micromolar IC50 values. In the current study, a series of 8-hydroxyquinoline derivatives were designed and synthesized as new MMP-2 and MMP-9 inhibitors. The most active compounds 5e and 5h not only displayed good inhibitory activities against MMP-2/9 with IC50 at submicromolar level, but also possessed potent anti-proliferative, anti-invasive and anti-angiogenesis activity in A549 cell line. Western blot also revealed that 5e and 5h down-regulate the expression of MMP-2 and MMP-9 in A549 cell line. Moreover, flow cytometry analysis indicated that compound 5e could promote apoptosis of A549 cells in vitro. Molecular docking analysis also revealed favorable binding modes of 5e in the active sites of MMP-2 and MMP-9.
- Chen, Chen,Yang, Xinying,Fang, Hao,Hou
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- SYNERGISTS
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Compounds of formula (I): wherein Ar represents an, optionally substituted, aryl or heteroaryl group, R represents an, optionally substituted, aryl or heteroaryl group, an optionally substituted straight or branched chain C1.10-alkyl, R1/
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Page/Page column 43-44
(2011/10/13)
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- Pd(quinoline-8-carboxylate)2 as a low-priced, phosphine-free catalyst for heck and suzuki reactions
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(Chemical Equation Presented) N,O-Bidentate compounds were systematically evaluated as phosphine-free ligands for Pd-catalyzed C-C bond-formation reactions through kinetic measurements. Pd(quinoline-8-carboxylate)2 was identified as one of the most efficient, yet still low-priced, phosphine-free catalysts for Heck as well as Suzuki reactions of unactivated aryl bromides with high turnover numbers up to ca. 10,000.
- Cui, Xin,Li, Juan,Zhang, Zhi-Ping,Fu, Yao,Liu, Lei,Guo, Qing-Xiang
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p. 9342 - 9345
(2008/03/13)
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- Amphiphilic compounds for sequential monolayer deposition
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Amphiphilic compounds and oligomers and polymers derived therefrom suitable for Langmuir Blodgett deposition having the general formula where M is a molecular moiety., x and y may be the same or different and are between 1 and 6, preferably 2 or 3,B1
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