13247-79-5Relevant academic research and scientific papers
The steric hindrance controlled [2]pseudorotaxanes constructed by V-type stilbene dyes?CB[7]
Gu, Qijing,He, Zihui,Pan, Qianxia,Lin, Ziyi,Sun, Jie,Wang, Qiang,Wang, Haibo
, p. 69 - 79 (2019)
In this paper, five V-type stilbene dyes (VD, 1a-1e) that had unchanged dimethylamino phenylethenyl (DMPE) arm as inclusive location with CB[7] and another arm with different steric hindrance aryloxyethyl (AE) group were designed and synthesized. Their inclusive characteristics and stability to CB[7] were studied. Fluorescence spectroscopy and 1H NMR method were used respectively to study the inclusive characteristics of 1a?CB[7], 1b?CB[7], 1c?CB [7], 1d?CB[7] and 1e?CB[7]. Fitting curves results of fluorescent titration indicated that 1:1 complexes between CB[7] and VD were constructed, and their inclusive constants were calculated respectively. The order of inclusive constants K1a?CB[7]>?K1b?CB[7]>?K1c?CB[7] >?K1d?CB[7] was consistent with the magnitude of the steric hindrance, however, 1e did not include with CB[7]. Therefore, a series of steric hindrance controlled [2]pseudorotaxanes were constructed.
Synthesis of new chalcone-based homoserine lactones and their antiproliferative activity evaluation
Yu, Bin,Liu, Haoyue,Kong, Xiaoyan,Chen, Xinli,Wu, Chunli
, p. 500 - 511 (2019)
Three series of new homoserine lactone analogs were efficiently synthesized starting from methionine and further evaluated for their antiproliferative activity against different cancer cell lines. Among these compounds, some of the chalcone containing compounds 6a-n showed acceptable antiproliferative activity against prostate cancer cells DU145 and PC-3 with the IC50 values less than 10 μM. Compounds 6c, 6e and 6h inhibited growth of DU145 and PC-3 cells at low micromolar levels with the IC50 values ranging from 3.0 to 5.0 μM, much more potent than natural OdDHL. Compound 6e concentration-dependently inhibited colony formation and cell migration of DU145 cells. A synergistic effect on the growth inhibition and the apoptosis of DU145 cells was observed when compound 6e was used in combination with TRAIL. OdDHL or 6e treatment concentration-dependently activated TRAIL death receptor DR5 which may account for the observed synergistic effect of 6e or OdDHL with TRAIL on the growth inhibition and cell apoptosis. Compound 6e also inhibited migration of DU145 cells in a time- and concentration-dependent manner. The data suggest that quorum sensing molecules OdDHL and 6e may improve the sensitivity of DU145 cells toward TRAIL via activating DR5, compound 6e may be used as a potential lead compound for developing new TRAIL receptor agonists.
Design, synthesis and biological evaluation of dual Bcl-2/Mcl-1 inhibitors bearing 2-(1H-indol-4-yl)benzoic acid scaffold
Niu, Qun,Deng, Hongguang,Zhang, Zhenwei,Xu, Qinhao,Luan, Shenglin,Huang, Min,Liu, Dan,Zhao, Linxiang
supporting information, (2021/07/06)
The anti-apoptotic protein inhibitors of the B cell lymphoma 2 (Bcl-2) family have been developed as new anticancer therapies. Numerous studies illustrated the great potential in the development of dual Bcl-2/myeloid cell leukemia 1 (Mcl-1) inhibitors. Herein, we reported a series of Bcl-2/Mcl-1 inhibitors that optimized from a hit compound 1 via structure-based rational design. The biological evaluation suggested that most compounds exhibited potent binding affinities at submicromolar to both Bcl-2 and Mcl-1 without any Bcl-xL binding affinities, especially compound 9o, with a Ki value of 0.07 μM to Mcl-1 and 0.66 μM to Bcl-2, that has great potential for developing dual inhibitors targeting Bcl-2 and Mcl-1.
Synthesis, antimicrobial evaluation, and in silico studies of quinoline—1H-1,2,3-triazole molecular hybrids
Awolade, Paul,Cele, Nosipho,Kerru, Nagaraju,Singh, Parvesh
, p. 2201 - 2218 (2020/06/17)
Abstract: Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline—1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed azide-alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC). Antimicrobial evaluation identified compound 16 as the most active hybrid in the library with a broad-spectrum antibacterial activity at an MIC80 value of 75.39?μM against methicillin-resistant S. aureus, E. coli, A. baumannii, and multidrug-resistant K. pneumoniae. The compound also showed interesting antifungal profile against C. albicans and C. neoformans at an MIC80 value of 37.69 and 2.36?μM, respectively, superior to fluconazole. In vitro toxicity profiling revealed non-hemolytic activity against human red blood cells (hRBC) but partial cytotoxicity to human embryonic kidney cells (HEK293). Additionally, in silico studies predicted excellent drug-like properties and the importance of triazole ring in stabilizing the complexation with target proteins. Overall, these results present compound 16 as a promising scaffold on which other molecules can be modeled to deliver new antimicrobial agents with improved potency. Graphic abstract: [Figure not available: see fulltext.].
DOPAMINE D2 RECEPTOR LIGANDS
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Page/Page column 126, (2016/07/05)
The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.
Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I)
Guo, Xiaoke,Ma, Xianglei,Yang, Qian,Xu, Jing,Huang, Lu,Jia, Jianmin,Shan, Jiaojiao,Liu, Li,Chen, Weilin,Chu, Hongxi,Wei, Jinlian,Zhang, Xiaojin,Sun, Haopeng,Tang, Yiqun,You, Qidong
supporting information, p. 89 - 94 (2014/06/09)
Kv1.5 potassium channel is an efficacious and safe therapeutic target for the treatment of atrial fibrillation (AF), the most common arrhythmia that threatens human. Herein, by modifying the hit compound 7k from an in-house database, 48 derivatives were synthesized for the assay of their Kv1.5 inhibitory effects by whole cell patch clamp technique. Six compounds which showed better potency than the positive compound dronedarone were selected for the next evaluation of their drug-like properties. Compound 8 exhibited balanced solubility and permeability. It also showed acceptable pharmacodynamics profile with very low acute toxicity. Taking all these data into account, compound 8 can serve as a promising lead for the development of novel therapeutic agent for the treatment of AF.
SUBSTITUTED BENZOFURAN, BENZOTHIOPHENE AND INDOLE MCL-1 INHIBITORS
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Paragraph 234, (2014/04/04)
The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.
NOVEL ANTIMICROBIAL COMPOUNDS
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Page/Page column 17, (2013/04/10)
A new class of biotin protein ligase (BPL) inhibitors that have antibacterial activity against multiple Staphylococcus aureus isolates, including clinically important methicillin-resistant S. aureus (MRSA) are disclosed that are non-toxic.
Synthesis, biological activity evaluation and molecular modeling study on the new isoconessimine derivatives as acetylcholinesterase inhibitors
Jin, Guofei,Yang, Zhongduo,Xue, Weiwei,Sheng, Jie,Shi, Yin,Yao, Xiaojun
, p. 1228 - 1233 (2013/10/21)
New isoconessimine derivatives were synthesized from conessine (1) and evaluated as acetylcholinesterase (AChE) inhibitors. The derivatives were prepared via two reaction steps, N-demethylation and nucleophilic substitution. All of the synthesized derivatives exhibited more potential anti- acetylcholinesterase activities than conessine (1) (IC50=16 μmol·L-1) and isoconessimine (2) (IC50>300 μmol·L-1). Compound 7b (3β-[methyl-[2-(4-nitrophenoxy) ethyl]amino]con-5-enine) showed the most potent inhibitory activity with an IC50 of 110 nmol/L which is close to that of reference compound huperzine A (IC50=70 nmol/L). The mode of AChE inhibition by 7b was reversible and non-competitive. In addition, molecular modeling was performed to explore the binding mode of inhibitor 7b at the active site of AChE and the results showed that 7b could be docked into the acetylcholinesterase active site and compound 7b had hydrophobic interactions with Trp279 and Leu282. A series of 3-N-aryloxyethyl substitutional isoconessimine derivatives were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. All of the synthesized derivatives exhibited potential anti-acetylcholinesterase activities with IC50 values at micromolar to sub-micromolar range. 7b showed the most potent inhibitory activity with an IC50of 110 nmol/L. The molecular docking results showed that 7b can be well docked into the active site of acetylcholinesterase. Copyright
7-NONSUBSTITUTED INDOLE MCL-1 INHIBITORS
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Page/Page column 88, (2008/12/08)
Compounds of formula (I) which inhibit the activity of anti-apoptotic Mcl-1 protein, compositins containing the compounds, and methods of treating diseases involving overexpressed or unregulated Mcl-1 protein are disclosed.
