1830-56-4Relevant academic research and scientific papers
The effects of novel heme oxygenase inhibitors on the growth of Pseudomonas aeruginosa
Zhao, Jingming,Liang, Dongdong,Robinson, Elizabeth,Xue, Fengtian
, p. 64 - 67 (2019)
Objectives: This study was aimed to develop small molecule inhibitors of the P. aeruginosa heme oxygenase (pa-HemO) as potential treatment of infections caused by P. aeruginosa. Methods: New compounds were designed based on the crystal structure of pa-HemO. The binding affinities (KD) were determined using intrinsic fluorescence quenching assays. The anti-microbial effects of the new compounds was evaluated by minimal inhibitory concentration 50% (MIC50). Results: Eleven compounds were synthesized as potential pa-HemO inhibitors. New compounds demonstrated KD values ranging from 1.5 to 180 μM, and MIC50 values ranging from 26 to 260 μg/mL. The compounds had good affinity with HemO and promising anti-microbial effects on P. aeruginosa. Conclusions: The new inhibitors described herein can inhibit the growth of P. aeruginosa via the inhibition of pa-HemO. There may be broad prospects for HemO inhibitors to treat P. aeruginosa related infections.
Ratiometric fluorescence assay for butyrylcholinesterase activity based on a hemicyanine and its application in biological imaging
Ding, Caifeng,Gao, Jian,Li, Jiajia,Liu, Haihong,Wan, Chenyang,Zhang, Peng,Zhang, Qian
, (2021/10/14)
Butyrylcholinesterase (BChE) is an esterase expressed by the liver, which is released into the plasma immediately. The activity of BChE in the serum is a sensitive indicator for determining the protein synthesis function of liver cells. Therefore, the development of high-efficiency chemical tools for detecting BChE is in urgent need. In this work, based on the ingenious combination of specific BChE enzymatic reaction, a ratiometric fluorescence probe was established to easily achieve the determination of BChE with high sensitivity with LOD calculated as low as 0.077 μg/mL. This probe also possesses a superior selectivity to BChE without the interference of other biological species even acetylcholinesterase (AChE), which gives it great potential to work for sensing in biological samples. The accurate IC50 (0.195 mM) of iso-OMPA, a specific inhibitor of BChE, could also be examined, indicating the excellent performance in elucidating inhibitory efficacy. In addition, the probe can be used for fluorescence imaging of BChE activity in living cells as well as animal tissues. These advantages indicate that the probe has important practical value for the monitoring of BChE activity.
NTR-1 response type fluorescent probe based on benzoindole as well as preparation method and application thereof
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Paragraph 0036-0038, (2021/04/10)
The invention discloses an NTR-1 response type fluorescent probe based on benzoindole as well as a preparation method and application of the NTR-1 response type fluorescent probe. The structure of the NTR-1 response type fluorescent probe is as defined in the specification. The method comprises the following steps: subjecting p-hydroxybenzaldehyde to reacting with p-nitrobenzyl bromide to synthesize a stable intermediate NFP-1-M connected through ether bonds, and condensing 1-ethyl-2-methylbenzo[cd]indole-1-chloride with the intermediate NFP-1-M to generate the probe NFP-1. The probe can be used for measuring the hypoxia degree of a cell, and is beneficial to early diagnosis of tumors and the like.
Palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamines with alkyl chloroformates
Shi, Yaqi,Wu, Yangjie,Yang, Fan
, p. 4628 - 4637 (2020/07/04)
A simple and efficient protocol for palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamine derivatives with alkyl chloroformates has been developed, exhibiting broad functional group tolerance, high regioselectivity, and oxidant-free conditions. Furthermore, the reaction features its ease of further functionalization and transformation. For example, the concise synthesis of one BET bromodomain inhibitor was accomplished via benz[cd]indol-2(1H)-one after multistep transformations from the obtained alkoxycarbonylation product. In addition, the control experiments suggest that the reaction might involve a radical process and the C-H bond cleavage might not be involved in the rate-determining step.
NEAR INFRARED (NIR) LASER PROCESSING OF RESIN BASED ARTICLES
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Paragraph 0115; 0125-0127, (2020/02/06)
A near infrared (NIR) laser processable resin based article comprising a specific optothermal converting. The specific optothermal converting has an improved thermal stability and therefore renders the preparation of the resin based article more reliable.
Cobalt-Catalyzed Direct Carbonylative Synthesis of Free (NH)-Benzo[ cd]indol-2(1 H)-ones from Naphthylamides
Ying, Jun,Fu, Lu-Yang,Zhong, Guoqiang,Wu, Xiao-Feng
, p. 5694 - 5698 (2019/07/08)
A cobalt-catalyzed C-H carbonylation of naphthylamides for the synthesis of benzo[cd]indol-2(1H)-one scaffolds has been developed. The reaction employs a traceless directing group and uses benzene-1,3,5-triyl triormate as the CO source, affording various free (NH)-benzo[cd]indol-2(1H)-ones in moderate to high yields (up to 88%). Using this protocol, the total synthesis of BET bromodomain inhibitors A and B was accomplished as well.
NEAR INFRARED (NIR) LASER PROCESSING
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Paragraph 0109-0110, (2019/06/23)
A method of near infrared (NIR) laser processing a resin based article comprising the steps of applying a composition comprising a specific optothermal converting agent on a surface of the article, and exposing at least part of the applied optothermal converting agent with a NIR laser. The specific optothermal converting has an improved stability towards the environment and therefore renders the laser processing method more reliable.
NIR TO SWIR FLUORESCENT COMPOUNDS FOR IMAGING AND DETECTION
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Paragraph 0113; 0127, (2019/04/18)
This disclosure provides a family of compounds that absorb and fluoresce in the short wave infrared region (SWIR, optionally 1000 nm to 1300 nm), including hydrophilic compounds that exhibit absorption and emission spectral profiles in aqueous solutions substantially similar to those observed in organic solvents such as methanol or DMSO. The compounds can be chemically linked to biomolecules including proteins, nucleic acids, and therapeutic small molecules. The compounds are useful for imaging in a variety of medical, biological and diagnostic applications, including SWIR in vivo imaging of regions of interest within a mammal.
Discovery of Benzo[ cd]indol-2(1 H)-ones and Pyrrolo[4,3,2- de]quinolin-2(1 H)-ones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain with Potential High Efficiency against Acute Gouty Arthritis
Jiang, Fei,Hu, Qinghua,Zhang, Zhimin,Li, Hongmei,Li, Huili,Zhang, Dewei,Li, Hanwen,Ma, Yu,Xu, Jingjing,Chen, Haifang,Cui, Yong,Zhi, Yanle,Zhang, Yanmin,Xu, Junyu,Zhu, Jiapeng,Lu, Tao,Chen, Yadong
, p. 11080 - 11107 (2019/12/24)
The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo[cd]indol-2(1H)-ones and pyrrolo[4,3,2-de]quinolin-2(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.
Design, synthesis and biological evaluation of benzo[cd]indol-2(1H)-ones derivatives as BRD4 inhibitors
Feng, Yuxin,Xiao, Senhao,Chen, Yantao,Jiang, Hao,Liu, Na,Luo, Cheng,Chen, Shijie,Chen, Hua
, p. 264 - 273 (2018/05/22)
Compound 1 bearing with benzo [cd]indol-2(1H)-one scaffold was identified as an effective BRD4 inhibitor through the AlphaScreen-based high-throughput screening and its high-resolution crystal structure with BRD4_BD1 protein. A series of 48 compounds were designed and synthesized by structural optimization on compound 1. All the compounds have been evaluated for their BRD4 inhibitory activities. The results showed that compounds 23, 24, 28 and 44 are the most potential ones with the IC50 values of 1.02 μM, 1.43 μM, 1.55 μM and 3.02 μM, respectively. According to their co-crystal structures in complex with BRD4_BD1 and the protein thermal shift assays, the binding modes were revealed that the additional indirect hydrogen bonds and hydrophobic interactions make such four compounds more active than 1 against BRD4. Furthermore, compounds 1, 23 and 44 were chosen to evaluate for their antiproliferative activities on the MLL-AF4-expression acute leukemia cell line (MV4-11), other cancer cell lines (MDA-MB-231, A549, 22Rv1) and the non-cancer cell lines (HUV-EC-C, MRC5, RPTEC). The results showed that these compounds exhibited good and selective inhibitory activities against MV4-11 cells with the IC50 values of 11.67 μM, 5.55 μM, and 11.54 μM, respectively, and could act on the cell proliferation by blocking cell cycle at G1 phase. They could markedly down-regulate the expressions of the c-Myc, Bcl-2 and CDK6 oncogenes in MV4-11 in the qRT-PCR and western blot studies, which further demonstrated that compound 1 and its derivatives could serve as a promising therapeutic strategy for MLL leukemia by targeting BRD4_BD1 protein.
