670-80-4Relevant articles and documents
Design, synthesis, and evaluation of semi-conservative mono-carbonyl analogs of curcumin as anti-inflammatory agents against lipopolysaccharide-induced acute lung injury
Dong, Lili,Zheng, Suqing,Zhang, Yali,Jiang, Xin,Wu, Jianzhang,Zhang, Xiaoqin,Shan, Xiaoou,Liang, Dandan,Ying, Shilong,Feng, Jianpeng,Liang, Guang
, p. 1544 - 1553 (2015)
Acute lung injury (ALI), one of a few severe diseases with high mortality, cannot be tackled by any effective therapies so far. Pro-inflammatory cytokines play an essential role in the pathogenesis of ALI. In order to discover novel anti-inflammatory agents against ALI, 37 semi-conservative mono-carbonyl analogs of curcumin (ScMACs) were designed, synthesized and screened for anti-inflammatory activities. The majority of these compounds exhibited remarkable inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Among them, compounds 6, 7, 10 and 18, efficiently inhibited the secretion of TNF-α and IL-6 in a dose-dependent manner. The most potent analog, compound 6, prevented the LPS-induced elevation of inflammatory gene expression, and alleviated the lung inflammatory cell infiltration and histopathological changes in vivo. Therefore, compound 6 is a potential lead for developing new anti-inflammatory candidate drugs against LPS-induced ALI.
Lanthanoid(III) Trichloride-Tin(II) Chloride mediated Cycloaddition Reaction of α,α'-Dibromo Ketones with 1,3-Dienes or Enamines
Fukuzawa, Shin-ichi,Fukushima, Masakazu,Fujinami, Tatsuo,Sakai, Shizuyoshi
, p. 2348 - 2352 (1989)
The reaction of α,α'-dibromo ketones with 1,3-dienes in the presence of CeCl3-SnCl2 in tetrahydrofuran is found to give the corresponding cycloadduct in fair to good yields under mild conditions.Furan and cyclopentadiene serve as highly efficient receptors of the oxallyl intermediate to give bicyclic cycloadducts.The reaction of 2,4-dibromo-3-pentanone with isoprene gives both and cycloadducts. Cycloaddition proceeds similarly with enamines to afford 2-cyclopenten-1-ones after treatment with 3percent ethanolic NaOH solution.
Thermal [2 + 2] cycloaddition of morpholinoenamines with C60 via a single electron transfer
Mikie, Tsubasa,Asahara, Haruyasu,Nagao, Kazuaki,Ikuma, Naohiko,Kokubo, Ken,Oshima, Takumi
, p. 4244 - 4247 (2011)
The thermal reaction of C60 with five- and six-membered morpholinocycloalkenes in refluxing toluene exclusively gave the [2 + 2] cycloadducts in high yields. However, a seven-membered homologue sluggishly reacted with C60 because of the increasing steric hindrance. This cycloaddition reaction is likely to proceed via a single electron transfer (SET), a radical-coupling, and subsequent ion cyclization rather than the prior proton transfer between the radical ions.
Synthesis and Anti-Inflammatory Evaluation of Novel C66 Analogs for the Treatment of LPS-Induced Acute Lung Injury
Feng, Jianpeng,Xiao, Bing,Chen, Wenbo,Ding, Ting,Chen, Lingfeng,Yu, Pengtian,Xu, Fengli,Zhang, Huajie,Liu, Zhiguo,Liang, Guang
, p. 753 - 763 (2015)
We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF-α and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce the W/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, COX-2, ICAM-1 and VCAM-1, in the Beas-2B cells after LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.
Reaction of enamines with semicarbazone-based amidoalkylating reagents: A straightforward synthesis of annulated 1-aminopyrimidin-2-one derivatives
Fesenko, Anastasia A.,Shutalev, Anatoly D.
, (2021)
An efficient synthesis of 1-arylideneamino-substituted hexahydro-1H-cyclopenta[d]pyrimidin-2-ones and octahydroquinazolin-2-ones has been developed. The synthesis involves a stereo- and regioselective cascade reaction of the corresponding 4-(tosylmethyl)semicarbazones with 1-morpholinocyclopentene or 1-morpholinocyclohexene to give predominantly bicyclic pyrimidines with an exocyclic C[dbnd]C double bond (80–97%). The later undergo rapid isomerization when heated in THF in the presence of TsOH to form bicyclic pyrimidines with a significant predominance of those with an endocyclic C[dbnd]C double bond (90–97%).
Synthesis and in-vitro anti-cancer evaluations of multi-methoxylated asymmetrical diarylpentanoids as intrinsic apoptosis inducer against colorectal cancer
Leong, Sze Wei,Chia, Suet Lin,Abas, Faridah,Yusoff, Khatijah
, (2020)
In the present study, a series of nine stable 3,4,5-methoxylphenyl-containing asymmetrical diarylpentanoids, derivatives of curcuminoids, have been synthesized, characterized and evaluated for their in-vitro anti-cancer potential against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, LoVo and SW620, HT29, RKO and NCI-H508, respectively. Structure-activity relationship study on cytotoxicity of tested compounds suggested that the presence of meta-hydroxyl and adjacent dimethoxyl groups are crucial for enhanced cytotoxicity of diarylpentanoids. Among the evaluated analogs, 8 has been identified as the lead compound due to its highest chemotherapeutic index of 9.9 and nano molar scale cytotoxicity against SW620 and RKO. Colonies formation and cell cycle analyses on 8-treated RKO cells showed that 8 exhibits strong anti-proliferative activity by inducing G2/M-phase cell arrest. Subsequent flow cytometry based annexin-V and DCFHDA studies suggested that 8 could induce apoptosis through intracellular ROS-dependent pathway. Further Western blot studies confirmed that 8 has induced intrinsic apoptosis in RKO cells through the up-regulations of Bad and Bax pro-apoptotic proteins and down-regulations of Bcl-2 and Bcl-xL pro-survival proteins. In all, the present results suggest that 8 could be a potent lead which deserves further modification and investigation in the development of small molecule-based anti-colorectal cancer agents.
Indium(III) chloride catalyzed in situ generation of enamines and cyclization with imines: A novel route for synthesis of hexahydroxanthene-9-N- arylamines
Anniyappan, Marimuthu,Muralidharan,Perumal, Paramasivan T.,Vittal, Jagadese J.
, p. 2965 - 2969 (2004)
A simple, efficient, and novel method has been developed for the synthesis of hexahydroxanthene-9-N-arylamine derivatives through a one-pot reaction of cyclohexanone and morpholine with salicylaldehyde imines in the presence of indium(III) chloride as a catalyst. 1-(4-Morpholino)-cyclohexene enamine prepared in situ from cyclohexanone and morpholine in presence of 20mol% InCl3 in acetonitrile under reflux condition was used without further purification, for the cyclization reaction with salicylaldehyde Schiff's bases.
A newly designed curcumin analog Y20 mitigates cardiac injury via anti-inflammatory and anti-oxidant actions in obese rats
Qian, Yuanyuan,Zhong, Peng,Liang, Dandan,Xu, Zheng,Skibba, Melissa,Zeng, Chunlai,Li, Xiaokun,Wei, Tiemin,Wu, Lianpin,Liang, Guang
, (2015)
Obesity is strongly associated with the cause of structural and functional changes of the heart in both human and animal models. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiac disorders. Curcumin is a natural product from Curcuma Longa with multiple bioactivities. In our previous study, in order to reach better anti-inflammatory and anti-oxidant dual activities, we designed a new mono-carbonyl curcumin analog, Y20, via the structural modification with both trifluoromethyl and bromine. This study was designed to investigate the protective effects of Y20 on obesity-induced cardiac injury and its underlying mechanisms. In high fat diet-fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis. Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg. The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Taken together, these results suggest that Y20 may have a great therapeutic potential in the treatment of obesity-induced cardiac injury using Nrf2 and NF-κB as the therapeutic targets for treating obesity-related disorders.
Enamine Organocatalysts for the Thiol-Michael Addition Reaction and Cross-Linking Polymerizations
Sinha, Jasmine,Soars, Shafer,Bowman, Christopher N.
, p. 1693 - 1701 (2021/02/16)
This article describes an efficient enamine organocatalyzed thiol-Michael click reaction and its broad application in cross-linking polymerizations. A series of enamines was shown to catalyze the thiol-Michael reaction via a nucleophilic pathway. By varying the amines as well as the ring size of the ketones, enamines were designed with broad ranges of nucleophilic character ranging from 11 to 17 on the Mayr nucleophilicity scale. Upon evaluating the enamines' organocatalytic effect on the kinetics of reactions involving a thiol and Michael acceptor, wherein butyl 3-mercaptopropionate and 1-hexyl acrylate were used as model reactants, enamines were shown to outperform their base analogs. The efficiency and overall reaction yields, ranging from 11 to 92% based on the thiol conversion, were highly dependent upon the nucleophilicity of the enamines employed. Interestingly, in situ formation of an enamine via photo-deprotection of an amine in the presence of cyclic ketones facilitated the thiol-Michael reaction efficiently while simultaneously enabling higher functional group conversion. This efficiency in the reaction kinetics and conversion was extended to multifunctional derivatives, which resulted in the formation of highly cross-linked polymers.
Three-Step One-Pot Process of 3-Methyl-5-Benzofuranol from Amine, Aldehydes, and p-Benzoquinone
Liang, Chaoming,Sun, Maolin,Shen, Xinyuan,Shan, Chao,Wang, Weijuan,Cheng, Ruihua,Ye, Jinxing
, p. 810 - 816 (2021/04/05)
3-Methyl-5-benzofuranol was prepared by a one-pot process from morpholine, propionaldehyde, and p-benzoquinone in 85-87% isolated yields. Avoiding the tedious multistep isolation and purification operations, this practical and efficient process dramatically enhanced the production efficiency as well as reduced the amount of chemical wastes of reaction. The scale-up results showed that the performance was maintained, suggesting potential large-scale applications. Furthermore, the synthesis strategy showed high efficiency for a wide range of aliphatic aldehydes and ketone derivatives.
