- Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity
-
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
-
-
- Sequential [3+2] annulation reaction of prop-2-ynylsulfonium salts and hydrazonyl chlorides: Synthesis of pyrazoles containing functional motifs
-
A novel sequential [3+2] annulation reaction has been developed using prop-2-ynylsulfonium salts and hydrazonyl chlorides, affording a series of pyrazoles with functional motifs that can be post modified in the preparation of various drugs or drug candidates. Further transformation and gram-scale operations could also be achieved efficiently. This journal is
- Jia, Tingting,Liu, Shourong,Shao, Jiaan,Shi, Tao,Wu, Zhaoxiao,Zeng, Linghui,Zhang, Chong,Zhang, Jiankang,Zhu, Huajian,Zhuang, Rangxiao
-
supporting information
p. 8460 - 8463
(2021/09/08)
-
- Nitrofuran drugs beyond redox cycling: Evidence of Nitroreduction-independent cytotoxicity mechanism
-
Nitrofurans (5-nitro-2-hydrazonylfuran as pharmacophore) are a group of widely used antimicrobial drugs but also associated to a variety of side effects. The molecular mechanisms that underlie the cytotoxic effects of nitrofuran drugs are not yet clearly understood. One-electron reduction of 5-nitro group by host enzymes and ROS production via redox cycling have been attributed as mechanisms of cell toxicity. However, the current evidence suggests that nitrofuran ROS generation by itself is uncapable to explain the whole toxic effects associated to nitrofuran consumption, proposing a nitro-reduction independent mechanism of toxicity. In the present work, a series of nitrated and non-nitrated derivatives of nitrofuran drugs were synthesized and evaluated in vitro for their cytotoxicity, ROS-producing capacity, effect on GSH-S-transferase and antibacterial activity. Our studies showed that in human cells non-nitrated derivatives were less toxic than parental drugs but, unexpectedly preserved the ability to generate intracellular ROS in similar amounts to nitrofurans despite not entering into a redox cycle mechanism. In addition, some non-nitrated derivatives although being uncapable to generate ROS exhibited the highest cell toxicity among all derivatives. Inhibition of cytosolic glutathione-S-transferase activity by some derivatives was also observed. Finally, only nitrofuran derivatives displayed antibacterial effect. Results suggest that the combined 2-hydrazonylfuran moiety, redox cycling of 5-nitrofuran, and inhibitory effects on antioxidant enzymes, would be finally responsible for the toxic effects of the studied nitrofurans on mammalian cells.
- Gallardo-Garrido,Cho,Cortés-Rios,Vasquez,Pessoa-Mahana,Araya-Maturana,Pessoa-Mahana,Faundez
-
-
- The use of enaminones and enamines as effective synthons for MSA-catalyzed regioselective synthesis of 1,3,4-tri- And 1,3,4,5-tetrasubstituted pyrazoles
-
In the present work, an efficient regioselective synthesis of 1,3,4-tri- and 1,3,4,5-tetrasubstituted pyrazoles via a methanesulfonic acid (MSA)-catalyzed reaction of hydrazones with enaminones or enamines is reported. Mechanistically, the formation of the title compounds involves the [2+3] cycloaddition of hydrazones with enaminones or enamines followed by aromatization with acid and oxygen. This convenient method under mild conditions with various hydrazones, enaminones, and enamines was well-tolerated to afford products in good to excellent yields. Compared with the literature methods, this strategy has advantages such as materials that are available economically, metal-free catalysis, excellent regioselectivity, and high efficiency.
- Duan, Liancheng,Zhou, Hui,Gu, Yucheng,Gong, Ping,Qin, Mingze
-
supporting information
p. 16131 - 16137
(2019/11/03)
-
- Nano BF3·SiO2: A green heterogeneous solid acid for synthesis of formazan dyes under solvent-free condition
-
A solvent-free, efficient and rapid approach for synthesis of formazan dyes was developed by diazotization of aromatic amines with NaNO2, nano silica-supported boron trifluoride (nano BF3·SiO2), then diazo coupling with aldehyde phenylhydrazones by grinding method at room temperature. This study aimed to overcome the limitations and drawbacks of the previous reported methods such as: low temperature, using corrosive and toxic acids and solvents, using buffer solutions, instability of aryl diazonium salts, modest yields, and long reaction times.
- Bamoniri, Abdolhamid,Mirjalili, Bi Bi Fatemeh,Moshtael-Arani, Naimeh
-
p. 272 - 278
(2014/07/22)
-
- Room temperature ionic liquid choline chloride-oxalic acid: A versatile catalyst for acid-catalyzed transformation in organic reactions
-
An efficient and facile synthesis of hydrazones, bis(indolyl)methanes and bis(4-hydroxycoumarin)methanes is facilitated by room temperature ionic liquid choline chloride-oxalic acid (ChCl:Ox). ChCl:Ox (10 mol%) efficiently catalyzes condensation of aldehydes with phenylhydrazine giving corresponding hydrazones in high yield (92-96%) within short reaction time of 3-5 min. Electrophilic cyclization reaction of indole and 4-hydroxy coumarin with aromatic aldehyde was effectively promoted by 30 mol% of ChCl:Ox giving corresponding bis(indolyl)arylmethanes and bis (4-hydroxycoumarin)methanes in good yield at room temperature. Procedure is very simple, solvent free and completely eliminates use of toxic acid catalyst. ChCl:Ox is biodegradable, can be recycled and reused without the loss of efficiency with respect to yield.
- Yadav, Urmiladevi Narad,Shankarling, Ganapati Subray
-
p. 137 - 141
(2014/01/17)
-
- Oxidized single-walled carbon nanotubes (swcns-cooh) as a new catalyst for the protection of carbonyl groups as hydrazones
-
Nano-materials are considered as suitable heterogeneous catalysts for many organic reactions. Herein oxidized carbon nanotube (SWCNTs-COOH) has been reported as a heterogeneous catalyst, for protection of carbonyl groups as hydrazones in EtOH at 80 C. The reactions proceed smoothly with good to excellent yields, and the SWCNTs-COOH used can be recycled.
- Borazjani, Maryam Kiani,Safaei, Hamid Reza,Panahandeh, Majid,Kiani, Ali Reza,Kiani, Masoumeh,Mofarahi, Masoud
-
p. 279 - 281
(2013/12/04)
-
- Synthesis of tetrahydropyridazines by a metal-carbene-directed enantioselective vinylogous N-H insertion/Lewis acid-catalyzed diastereoselective Mannich addition
-
A versatile cascade of reactions, triggered by RhII-catalyzed diazo decomposition followed by a vinylogous N-H insertion/Lewis acid catalyzed Mannich addition, that produces highly substituted 1,2,3,6-tetrahydropyridazines in up to 97% ee with high yield and diastereocontrol has been developed. Copyright
- Xu, Xinfang,Zavalij, Peter Y.,Doyle, Michael P.
-
supporting information
p. 9829 - 9833
(2012/11/07)
-
- Copper-mediated synthesis of substituted 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles via C-H functionalization/C-N/C-O bond formation
-
An efficient method for the transformation of N-benzyl bisarylhydrazones and bisaryloxime ethers to functionalized 2-aryl-N-benzylbenzimidazoles and 2-arylbenzoxazoles is described. The protocol involves a copper(II)-mediated cascade C-H functionalization/C-N/C-O bond formation under neutral conditions. Substrates having either electron-donating or -withdrawing substituents undergo the cyclization to afford the target heterocycles at moderate temperature.
- Guru, Murali Mohan,Ali, Md Ashif,Punniyamurthy, Tharmalingam
-
p. 5295 - 5308
(2011/08/05)
-
- Open vessel and cooling while heating microwave-assisted synthesis of pyridinyl N-Aryl hydrazones
-
We reported the first example of open vessel and cooling while heating microwave-assisted synthesis of pyridinyl N-aryl hydrazones. Compounds were prepared in excellent isolated yields (88-98%) in only 5 min, by reacting 4- and 2,4-(di)substituted phenylhydrazines, bearing both electron-donating (4-CH 3, 4-OCH3) and -withdrawing (4-Cl, 4-Br, 4-CF3, 4-NO2, 2,4-Cl2) groups with 2-, 3-, and 4-acetylpyridine. The method was successfully extended to other carbonyl compounds.
- La Regina, Giuseppe,Gatti, Valerio,Piscitelli, Francesco,Silvestri, Romano
-
experimental part
p. 2 - 6
(2011/04/15)
-
- Solubility of thiophene-, furan- and pyrrole-2-carboxaldehyde phenylhydrazone derivatives in 2.82 mol?L-1 aqueous DMSO at 298.15 K, inhibition of lymphoproliferation and tubulin polymerization: A study based on the scaled particle theory
-
In this work, the solubilities of nine phenylhydrazone derivatives in water and in 2.82 mol ? L-1 aqueous DMSO at 298.15 K, expressed on the molar fraction scale, are reported. The estimated value of the standard Gibbs energy for transferring t
- Alvarado, Ysaías J.,álvarez-Mon, Melchor,Baricelli, Joanna,Caldera-Luzardo, José,Cubillán, Néstor,Ferrer-Amado, Gladys,Hassanhi, Manzur,Marrero-Ponce, Yovani,Mancilla, Victoria,Rocafull, Miguel A.,San?Antonio-Sánchez, Mari?a Esther,Ojeda-Andara, José,Thomas, Luz E.
-
body text
p. 1099 - 1112
(2011/05/30)
-
- Polystyrene sulfonic acid catalyzed greener synthesis of hydrazones in aqueous medium using microwaves
-
An environmentally benign aqueous protocol for the synthesis of cyclic, bi-cyclic, and heterocyclic hydrazones using polystyrene sulfonic acid (PSSA) as a catalyst has been developed; the simple reaction proceeds efficiently in water in the absence of any
- Polshettiwar, Vivek,Varma, Rajender S.
-
p. 5649 - 5652
(2008/02/10)
-
- Parallel synthesis of pyrazolines on soluble polymer support
-
An efficient and rapid parallel liquid-phase synthesis of pyrazolines has been developed. The one-pot three-components reaction of polyethylene glycol (PEG)-supported acrylate 1, aldehyde 2 and aryl hydrazine 3 in the presence of chloramine-T in methanol gave the corresponding PEG-supported pyrazolines 5. Cleavage from the support under mild conditions afforded pyrazolines 6 in good yields (69-91%) and high purities (91-100%).
- Wang, Yan-Guang,Zhang, Jian,Lin, Xu-Feng,Ding, Han-Feng
-
p. 1467 - 1468
(2007/10/03)
-