- Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity
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Histone deacetylase 6 (HDAC6) has emerged as a critical regulator of many cellular pathways in tumors due to its unique structure basis and abundant substrate types. Over the past few decades, the role played by HDAC6 inhibitors as anticancer agents has sparked great interest of biochemists worldwide. However, they were less reported for gastric cancer therapy. In this paper, with the help of bioisosteric replacement, in-house library screening, and lead optimization strategies, we designed, synthesized and verified a series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors with promising anti-gastric cancer activities. Amongst, compound 9r displayed the best inhibitory activity towards HDAC6 (IC50 = 30.6 nM), with 128-fold selectivity over HDAC1. Further BLI and CETSA assay proved the high affinity of 9r to HDAC6. In addition, 9r could dose-dependently upregulate the levels of acetylated α-tubulin, without significant effect on acetylated histone H3 in MGC803 cells. Besides, 9r exhibited potent antiproliferative effect on MGC803 cells, and promoted apoptosis and suppressed the metastasis without obvious toxicity, suggesting 9r would serve as a potential lead compound for the development of novel therapeutic agents of gastric cancer.
- Zhang, Xin-Hui,Kang, Hui-Qin,Tao, Yuan-Yuan,Li, Yi-Han,Zhao, Jun-Ru,Ya-Gao,Ma, Li-Ying,Liu, Hong-Min
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- From Phenylhydrazone to 1H-1,2,4-Triazoles via Nitrification, Reduction and Cyclization
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Herein we report an annulation of phenylhydrazone via a tandem nitrification, reduction, cyclization protocol employing cobalt nitrate and 1,2-dichloroethane to produce substituted 1H-1,2,4-triazoles. Notably, 1,2-dichloroethane serves both the solvent and a hydrogen source for transfer hydrogenation. This methodology works under mild conditions, providing a direct approach for the synthesis of 1H-1,2,4-triazoles. (Figure presented.).
- Hao, Liqiang,Wang, Guodong,Sun, Jian,Xu, Jun,Li, Hongshuang,Duan, Guiyun,Xia, Chengcai,Zhang, Pengfei
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supporting information
p. 1657 - 1662
(2020/03/19)
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- Facile One-Pot Transformation of Primary Alcohols into 3-Aryl- and 3-Alkyl-isoxazoles and -pyrazoles
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Various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylisoxazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, NH 2 OH, and then NCS, followed by reaction with alkynes in the presence of Et 3 N. Similarly, various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylpyrazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, PhNHNH 2, and then NCS and decyl methyl sulfide, followed by reaction with alkynes in the presence of Et 3 N. Thus, both 3-aryl- and 3-alkylisoxazoles, and 3-aryl- and 3-alkylpyrazoles could be prepared from readily available primary alcohols in one pot under transition-metal-free conditions.
- Kobayashi, Eiji,Togo, Hideo
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p. 3723 - 3735
(2019/09/30)
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- Lewis acid–catalyzed green synthesis and biological studies of pyrrolo[3,4-c]pyrazoles in aqueous medium
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An environmentally benign approach in aqueous medium by means of Lewis acid catalyst affords a wide spectrum of pyrazoline derivatives in satisfactory yields. [3+2] cycloaddition reactions of substituted azomethine-N-imines to maleimide in aqueous medium at relatively high concentrations of Lewis acid catalyst have emerged as an environment friendly alternative to conventional solvents. Promising catalytic activity has been revealed by Lewis acid like Cu (NO3)2 in aqueous medium. The obvious features of this synthetic protocol were short reaction time, high efficiency, less hazardous synthesis by benign solvent, catalysis, modest workup, and a clean reaction methodology.
- Arjuna, Anania,Kaur, Manpreet,Singh, Baldev
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- Radical Addition of Hydrazones by α-Bromo Ketones to Prepare 1,3,5-Trisubstituted Pyrazoles via Visible Light Catalysis
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A novel efficient tandem reaction of hydrazones and α-bromo ketones is reported for the preparation of 1,3,5-trisubstituted pyrazoles by visible light catalysis. In this system, the monosubstituted hydrazones show wonderful reaction activity with alkyl radicals, generated from α-bromo ketones. A radical addition followed by intramolecular cyclization affords the important pyrazole skeleton in good to excellent yields. This efficient strategy under mild conditions with wide group tolerance provides a potential approach to the 1,3,5-trisubstituted pyrazoles.
- Fan, Xiu-Wei,Lei, Tao,Zhou, Chao,Meng, Qing-Yuan,Chen, Bin,Tung, Chen-Ho,Wu, Li-Zhu
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p. 7127 - 7133
(2016/08/30)
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- Microwave assisted one-pot tandem three-component synthesis of 2,4,5-triary1-2-4-dihydro-3H-1,2,4-triazol-3-one derivatives
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This work described a one-pot tandem three-component synthesis of 2,4,5-triaryl-2,4-dihydro-3H-1,2,4-triazol-3-ones using a simple reaction between phenylhydrazines, benzaldehydes and phenyl isocyanates under microwave irradiation and solvent-free conditi
- Mohammadi, Bagher,Adib, Mehdi
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p. 553 - 556
(2014/05/06)
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- 1, 3-Dipolar cycloaddition reactions: Synthesis of 5-benzyl-1-(2',4'- dibromophenyl)-3-(4''-substituted phenyl)-3a,4,6,6a-tetrahydro-1H, 5H-pyrrolo[3,4-c]pyrazole-4,6-dione derivatives
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1,3-Dipolar cycloaddition of nitrilimines 3 with N-benzyl maleimide 4 has provided 5-benzyl-1-(2',4'-dibromophenyl)-3-(4''-substituted phenyl)-3a,4,6,6a-tetrahydro-1H,5H-pyrrolo[3,4-c]pyrazole-4,6-dione derivatives 5 in excellent yield as the only isomer through a concerted pathway. Indian Academy of Sciences.
- Kaur, Manpreet,Singh, Baldev,Singh, Baljit
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p. 1529 - 1534
(2014/04/03)
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- A one-pot synthesis of bisarylhydrazones by Cu(I)-catalyzed aerobic oxidation
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An efficient Cu(I)-catalyzed one-pot synthesis of N-substituted (or NH) bisarylhydrazones is reported. A further cyclization reaction could occur towards the synthesis of benzimidazoles or triazoles with elevated temperature. A plausible alkylation-oxidation-alkylation mechanism is proposed based on experimental results and literature.
- Hu, Jiu-Rong,Zhang, Wan-Jia,Zheng, Da-Gui
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p. 9865 - 9869
(2013/10/22)
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- Medicinal uses of hydrazones
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Compounds having a structure according to Formula (I): are effective in a method of increasing erythropoietin and vascularization of tissue in a subject in need thereof.
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