1,5-Diphenyl-1,4-pentadiene-3-ones and cyclic analogues as antioxidative agents. Synthesis and structure-activity relationship

Sardjiman, S.S.; Reksohadiprodjo, M.S.; Hakim, Lawrence S.; Goot, H. van der; Timmerman, H.

doi:10.1016/s0223-5234(97)83288-6

Cited by 110 publications

(83 citation statements)

References 11 publications

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“…3,21,22 It is believed that the presence of the active methylene group and β-diketone moiety contributes to the instability of curcumin under physiological conditions, poor absorption and fast metabolism. 23 Recently, synthetic modifications of curcumin have been studied intensively in order to develop a molecule with enhanced properties and stability. [23][24][25][26] In the present study, a series of curcumin analogues with more stable structures were synthesized and tested for anti-inflammatory activity in vitro.…”

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confidence: 99%

“…23 Recently, synthetic modifications of curcumin have been studied intensively in order to develop a molecule with enhanced properties and stability. [23][24][25][26] In the present study, a series of curcumin analogues with more stable structures were synthesized and tested for anti-inflammatory activity in vitro. Several analogues showed an enhanced ability to inhibit lipopolysaccharide (LPS)-induced TNF-α and IL-6 in macrophages.…”

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confidence: 99%

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Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin

Liang

Chen

et al. 2008

Bioorganic & Medicinal Chemistry Letters

131

113

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Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The β-diketone moiety renders curcumin to be rapidly metabolized by aldoketo reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide (LPS)-induced TNF-α and IL-6 synthesis in macrophages.Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Fig. 1] is the major active constituent of turmeric, a yellow compound originally isolated from the plant Curcuma longa L. Tumeric has been widely used for centuries as a dietary spice and pigment. 1 In addition to its unique flavor and color, tumeric has been extensively used in traditional medicine in China and India, particularly as an anti-inflammatory agent. 2 During the last two decades, numerous studies have shown that curcumin has a variety of biological and pharmacological activities such as anti -carcinogen, immuno-modulation, anti-oxidant, antiangiogenesis, and chemo-prevention. 3-9 Recent studies have demonstrated that inflammation is implicated in the pathogenesis of various diseases including cancer, atherosclerosis, diabetes, fatty liver, rheumatoid arthritis, and inflammatory bowel disease. 10-13 Anti-inflammation is the major focus of current drug development. 14 Cytokines are local mediators produced by lymphocytes and macrophages as well as by epithelial and mesenchymal cells. 15 It has been demonstrated that cytokines are involved in a variety of biological processes and play a central role in the development of inflammation and immunity. TNF-α is a multifunctional cytokine produced primarily by activated monocytes/macrophages and plays a critical role in the initiation and continuation of inflammation and immunity. 16 It is well-known that TNF-α is a key proinflammatory cytokine in the pathogenesis of various inflammatory diseases and cancer. 13, 17 In addition to directly *Corresponding authors: Huiping Zhou: 1217 East Marshall Street, MSB#533, Richmond, VA 23298, USA. E-mail: hzhou@vcu.edu; Tel:804-828-6817; Fax:804-828-0676., Xiaokun Li: College of Pharmacy, Wenzhou Medical College., E-mail: xiaokunli@163.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In order to identify the crucial structural motifs leading to anti-inflammatory activity and gain insight into future directions for designing new analogues with better activity, thre...

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confidence: 99%

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confidence: 99%

Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin

Liang

Chen

et al. 2008

Bioorganic & Medicinal Chemistry Letters

131

113

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“…These compounds which still maintain the hydroxy moiety at aromatic rings show a substantial antioxidant activity. 18) The compounds resulting from these modification are named 1,5-diphenyl-1,4-pentadiene-3-one analogues, benzylidenecyclopentanone, and benzylidenecyclohexanone, respectively.…”

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Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells

2009

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Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is a natural yellow pigment isolated from the rhizomes of the plant Curcuma longa L. (turmeric). Its chemical structure is described in Fig. 1.1) The pharmacological effects of curcumin include anti-inflammatory, 2) antioxidant, 3) antiprotozoal, 4) antibacterial, 5) anticancer, 6) antihepatotoxic, 7) hypolipidemic, 8) and antifibrotic effects. 9) Curcumin showed no toxicity in acute toxicity studies in rats, guinea pigs, and monkeys, 10) as well as in humans. 11)Several prior studies have examined the effects of curcumin on allergic diseases. An ethyl acetate extract of Curcuma longa L., which contains curcuminnoids, exhibited a preventive effect in allergic type I and IV models.12) Furthermore, both the ethyl acetate extract of Curcuma longa L. and curcumin were found to decrease histamine release from mast cells. However the ethyl acetate extract of Curcuma longa L. had somewhat stronger activity than that of curcumin, which may have been due to the presence of curcumin derivatives.13) Several studies have also examined the anti-allergic activity of curcumin and curcumin-related compounds in relation to their antioxidant effects. Most of these compounds were shown to inhibit histamine release from rat basophilic leukemia (RBL-2H3) cells; however, histamine release was decreased by antioxidant compounds and by those that lacked antioxidant activity. The results suggested that the hydroxy moiety of curcumin is responsible for antioxidant activity and may also contribute to the inhibition of histamine release. 14) In a guinea pig model of airway hyperresponsiveness, curcumin at a dose of 20 mg/kg body weight significantly inhibited ovalbumin (OVA)-induced airway constriction and airway hyperactivity. 15)Although curcumin has a wide range of potentially beneficial pharmacological effects, its use is limited by the compounds instability. The stability of curcumin is strongly affected by factors such as pH and exposure to light.16) The kinetics of the pH-dependent degradation of curcumin in aqueous medium at various pH levels was studied by Tonnesen and Karlsen. 17) They found that curcumin in aqueous solution at pH less than 7 is quite stable, but with increasing pH, curcumin decomposes. The main decomposition products are ferulic acid and feruloylmethane, which rapidly undergo retro-aldol condensation to vanillin and acetone. The instability of curcumin at alkaline pH is caused by the active methylene moiety. Decomposition of curcumin can also occur as a result of light exposure, and this process is also mediated by the active methylene moiety; the degradation products include ferulic aldehyde, ferulic acid, dihydroxynaphthalene product, 4-vinylguaiacol, vanillin, and vanillic acid. 16,17) The modification of the middle site of curcumin to compounds such as the 1,4-pentadiene-3-ones, cyclopentanone, and cyclohexanone which lack the active methylene moiety and one carbonyl moiety of curcumin may show improved stability. These compounds which st...

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“…In our previous publication, there are almost fifty analogs curcumin that successfully been made (Sardjiman et al, 1997;Sardjiman et al, 2003;Sardjiman et al, 2004). These analogs have many different biological activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Tetrahydrohexagamavunon-5 and Tetrahydrohexagamavunon-7

Ritmaleni

Praditya

Wibowo

et al. 2015

Indonesian J. Pharm.

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Synthesis of Tetrahydrohexagamavunon-5 (THHGV-5) and Tetrahydrohexagamavunone-7 (THHGV-7) were prepared by catalytic hydrogenation reaction on Hexagamavunon-5 (HGV-5) and Hexagamavunone-7 (HGV-7) by using gas H 2 as source of hydrogen gas, Pd/C 10 % as metal catalyst and methanol as solvent at room temperature. According to previous study, Pd/C catalyst is more specific than other metal catalyst to reduce α,β-unsaturated double bond without reduction of its carbonyl functional group.

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1,5-Diphenyl-1,4-pentadiene-3-ones and cyclic analogues as antioxidative agents. Synthesis and structure-activity relationship

Cited by 110 publications

References 11 publications

Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin

Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin

Effects of Benzylidenecyclopentanone Analogues of Curcumin on Histamine Release from Mast Cells

Synthesis of Tetrahydrohexagamavunon-5 and Tetrahydrohexagamavunon-7

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