55458-67-8Relevant academic research and scientific papers
Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer
Ray, Anne-Marie,Salim, Nilshad,Stevens, Mckayla,Chitre, Siddhi,Abdeen, Sanofar,Washburn, Alex,Sivinski, Jared,O'Hagan, Heather M.,Chapman, Eli,Johnson, Steven M.
, (2021/05/13)
Over the past few decades, an increasing variety of molecular chaperones have been investigated for their role in tumorigenesis and as potential chemotherapeutic targets; however, the 60 kDa Heat Shock Protein (HSP60), along with its HSP10 co-chaperone, have received little attention in this regard. In the present study, we investigated two series of our previously developed inhibitors of the bacterial homolog of HSP60/10, called GroEL/ES, for their selective cytotoxicity to cancerous over non-cancerous colorectal cells. We further developed a third “hybrid” series of analogs to identify new candidates with superior properties than the two parent scaffolds. Using a series of well-established HSP60/10 biochemical screens and cell-viability assays, we identified 24 inhibitors (14%) that exhibited > 3-fold selectivity for targeting colorectal cancer over non-cancerous cells. Notably, cell viability EC50 results correlated with the relative expression of HSP60 in the mitochondria, suggesting a potential for this HSP60-targeting chemotherapeutic strategy as emerging evidence indicates that HSP60 is up-regulated in colorectal cancer tumors. Further examination of five lead candidates indicated their ability to inhibit the clonogenicity and migration of colorectal cancer cells. These promising results are the most thorough analysis and first reported instance of HSP60/10 inhibitors being able to selectively target colorectal cancer cells and highlight the potential of the HSP60/10 chaperonin system as a viable chemotherapeutic target.
Design, synthesis, antifungal activity and 3D-QSAR study of novel pyrazole carboxamide and niacinamide derivatives containing benzimidazole moiety
Si, Wei-Jie,Wang, Xiao-Bin,Chen, Min,Wang, Meng-Qi,Lu, Ai-Min,Yang, Chun-Long
, p. 3000 - 3010 (2019/02/17)
A series of novel pyrazole carboxamide and niacinamide derivatives containing a benzimidazole moiety were designed and synthesized as antifungal candidate agents. All target compounds were characterized by FTIR, 1H NMR, 13C NMR, HRMS and elemental analysis techniques. The structure of compound T1 was further confirmed by single crystal X-ray diffraction analysis. The antifungal activities of the target compounds were evaluated in vitro against four phytopathogenic fungi (namely Botrytis cinerea, Rhizoctonia solani, Fusarium graminearum and Alternaria solani) by the mycelium growth inhibition method. The bioassay results indicated that some of the compounds exhibited good antifungal activity against B. cinerea at 100 μg ML?1 compared to other three fungi. In order to better explore the structure-activity relationship (SAR), the EC50 values of target compounds against B. cinerea were measured and assessed. Subsequently, a 3D quantitative structure-activity relationship (3D-QSAR) study was carried out using the comparative molecular field analysis (CoMFA) technique based on the inhibitory activities of tested compounds against B. cinerea. Molecular modelling results revealed fine predictive ability with cross-validated q2 and non-cross-validated r2 values of 0.578 and 0.850, respectively.
Design, synthesis, DFT study and antifungal activity of the derivatives of pyrazolecarboxamide containing thiazole or oxazole ring
Yan, Zhongzhong,Liu, Aiping,Huang, Mingzhi,Liu, Minhua,Pei, Hui,Huang, Lu,Yi, Haibo,Liu, Weidong,Hu, Aixi
, p. 170 - 181 (2018/03/08)
Pyrazolecarboxamide fungicides are one of the most important classes of agricultural fungicides, which belong to succinodehydrogenase inhibitors (SDHIS). To discover new pyrazolecarboxamide analogues with broad spectrum and high activity, a class of new compounds of pyrazole carboxamide derivatives containing thiazole or oxazole ring were designed by scaffold hopping and bioisosterism, and 36 pyrazole carboxamide derivatives with antifungal activity were synthesized. Those compounds were evaluated against five phytopathogenic fungi, Gibberella zeae, Phytophythora capsici, Sclerotonia sclerotiorum, Erysiphe graminis and Puccinia sorghi. The results indicated that most of the compounds displayed good fungicidal activities, especially against E. graminis. Theoretical calculations were carried out at the B3LYP/6-31G (d, p) level and the full geometry optimization was carried out using the 6-31G (d, p) basis set, and the frontier orbital energy, atomic net charges, molecular docking were discussed, and the structure-activity relationships were also studied.
Design, Synthesis, and Acaricidal Activities of Novel Pyrazole Acrylonitrile Compounds
Huang, Danling,Huang, Mingzhi,Liu, Aiping,Liu, Xingping,Liu, Weidong,Chen, Xiaoyang,Xue, Hansong,Sun, Jiong,Yin, Dulin,Wang, Xiaoguang
, p. 1121 - 1128 (2017/03/27)
Using cyenopyrafen as the lead compound, a series of novel pyrazole acrylonitrile compounds were designed and synthesized via the reaction of butylphenylacetonitrile with the corresponding (substituted pyrazol-5-yl) methanone of pyrethroid alcohols in the presence of potassium tert-butoxide. These compounds showed prominent acaricidal activity against Tetranchus urticae. In particular, IIf, IIh, IIo, and IIp displayed excellent activities, which the median lethal concentrations were all lower 0.4 mg/L. In addition, the structure-activity relationship for the target compounds was discussed.
Design, synthesis and biological evaluation of 1H-pyrazole-5-carboxamide derivatives as potential fungicidal and insecticidal agents
Huang, Danling,Huang, Mingzhi,Liu, Weidong,Liu, Aiping,Liu, Xingping,Chen, Xiaoyang,Pei, Hui,Sun, Jiong,Yin, Dulin,Wang, Xiaoguang
, p. 2053 - 2061 (2017/09/30)
A series of novel 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety were designed and synthesized by a facile method, and their structures were characterized by 1H NMR, mass spectrometry and elemental analysis. Bioassay results showed that most of the title compounds showed potent fungicidal activities against Erysiphe graminis and insecticidal activity against Aphis fabae. Especially, compound 9b has EC50 values of 3.04 mg/L against Erysiphe graminis, of which the fungicidal activity is better than that of the commercial fungicide Thifluzamide and Azoxystrobinare; compound 9l has LC50 values of 3.81 mg/L against Aphis fabae, which was comparable with the commercial insecticide Tolfenpyrad. It is suggested that 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety could be considered as a precursor structure for further design of pesticides. Graphical Abstract: A series of novel 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety were designed and synthesized by a facile method, and their structures were characterized by 1H NMR, mass spectrometry and elemental analysis. Bioassay results showed that most of the title compounds showed potent fungicidal activities against Erysiphe graminis and insecticidal activity against Aphis fabae. Especially, compound 9b has EC50 values of 3.04 mg/L against Erysiphe graminis, of which the fungicidal activity is better than that of the commercial fungicide Thifluzamide and Azoxystrobinare; compound 9l has LC50 values of 3.81 mg/L against Aphis fabae, which was comparable with the commercial insecticide Tolfenpyrad. It is suggested that 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety could be considered as a precursor structure for further design of pesticides.[Figure not available: see fulltext.]
Synthesis and insecticidal activities of novel 1H-pyrazole-5-carboxylic acid derivatives
Huang, Danling,Liu, Aiping,Liu, Weidong,Liu, Xingping,Ren, Yeguo,Zheng, Xi,Pei, Hui,Xiang, Jun,Huang, Mingzhi,Wang, Xiaoguang
, p. 455 - 460 (2017/12/18)
Fourteen 1H-pyrazole-5-carboxylic acid derivatives containing oxazole and thiazole rings were synthesized and characterized by 1H NMR, mass spectrometry and elemental analysis. Most target compounds were obtained in overall yields in the range of 30-50%. The insecticidal activities of these new compounds against Aphis fabae were evaluated. The bioassays' results indicate that some of these compounds exhibit good activities, especially compound 7h which shows 85.7% mortality against A. fabae at a concentration of 12.5 mg/L. This activity is comparable to that of the commercial insecticide imidacloprid.
Copper-Catalyzed Divergent Trifluoromethylation/Cyclization of Unactivated Alkenes
Zheng, Jing,Deng, Ziyang,Zhang, Yan,Cui, Sunliang
supporting information, p. 746 - 751 (2016/03/09)
Most of the precedent copper-catalyzed trifluoromethylation reactions of unactivated alkenes concern terminal alkenes, and these processes are terminated in elimination, or nucleophilic addition, or semipinacol rearrangement, or C-H bond functionalization steps. In this study, we develop a trifluoromethylation method for both unactivated terminal and internal alkenes to enable divergent late-stage radical cyclization and achieve high molecular complexity. These cyclizations are well consistent with Baldwin's rule. Furthermore, a kinetic isotope effect (KIE) study and control reactions were conducted, and a plausible mechanism is proposed.
THERAPEUTIC COMPOUNDS AND USES THEREOF
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Paragraph 0383; 0402, (2014/09/03)
Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.
Kinase Inhibitors
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Page/Page column 79, (2008/06/13)
The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
COMPOUNDS HAVING AFFINITY FOR THE DOPAMINE D3 RECEPTOR AND USES THEREOF IN MEDICINE
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Page/Page column 27, (2010/02/15)
Compounds of formula (I) or a salt thereof are disclosed, wherein A, m R1, R2, R3, q, W1, W2, R4 and R5 are as defined in the description. Processes for preparation and uses of the compounds in medicine, for example for the treatment of schizophrenia or drug dependency, are also disclosed.
