A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts

Gosslau, Alexander; Chen, M; Ho, Ci-T; Chen, K Y

doi:10.1038/sj.bjc.6602300

Cited by 99 publications

(54 citation statements)

References 48 publications

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“…57,58 Resveratrol also elevates iNOS activity 59 and triggers p53-mediated apoptosis. 60 Resveratrol also inhibits HGF-and ROS-driven invasive capacity of a rat ascites hepatoma cell line AH109A in culture. 61 It also inhibits the growth of H22 cells in culture.…”

Section: Liver Cancermentioning

confidence: 99%

Resveratrol: A multitargeted agent for age-associated chronic diseases

Harikumar¹,

Aggarwal²

2008

Cell Cycle

485

339

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Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g., NFκB, STAT3, HIF-1α, β-catenin and PPAR-γ), suppress the expression of antiapoptotic gene products (e.g., Bcl-2, Bcl-X L , XIAP and survivin), inhibit protein kinases (e.g., src, PI3K, JNK and AKT), induce antioxidant enzymes (e.g., catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. Efforts are also underway to improve its activity in vivo through structural modification and reformulation. Our review describes various targets of resveratrol and their therapeutic potential.

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Section: Liver Cancermentioning

confidence: 99%

Resveratrol: A multitargeted agent for age-associated chronic diseases

Harikumar¹,

Aggarwal²

2008

Cell Cycle

485

339

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“…The stilbene scaffold is abasic element for anumber of natural and synthetic compounds, which show avariety of biological activities [2][3][4]. In order to obtain further information on structureactivity relationships, we have designed and synthesized aseries of O-methylated stilbenes and their derivatives.…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of (E)-1-(4-hydroxyphenyl)-2-(3,4,5-trimethoxyphenyl)- ethene, C17H18O4, a trans-stilbene

Guo¹,

Li²,

Wang³

et al. 2008

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialAll reagents were commercially available and used without further purification. The title compound was synthesized according to [1]. Crystals of good quality suitable for X-ray crystallographic analysis were grown from anhydrous ethanol after amonth. DiscussionThe stilbene scaffold is abasic element for anumber of natural and synthetic compounds, which show avariety of biological activities [2][3][4]. In order to obtain further information on structureactivity relationships, we have designed and synthesized aseries of O-methylated stilbenes and their derivatives.In the crystal structure of the title compound, the bond lengths and angles are closely similar to that of stilbene itself and its derivatives [5,6]. There is an anomalously short ethylene bond with the value of 1.321(3) Å,compared to the normal conjugated ethylene bond of 1.38 Å [7]. This was attributed to orientational disorder and dynamical disorder due to torsional vibration of the C-phenyl bonds in adirection perpendicular to the molecular plane [8,9]. The C4-C7 and C8-C9 bonds [1.465(3) and 1.468(3) Å, respectively] are relatively short compared with an ormal C(sp 3 )-C(sp 3 )s ingle bond of 1.54 Å [8]. In addition to the known bond shortening due to the different hybridization of the carbon atoms (sp 2 vs. sp 3 ), this may indicate some resonance and partial double bond character of C4-C7 and C8-C9. As aconsequence, the stilbene skeleton is approximately planar, as evidenced by the largest deviation from the mean plane being 0.152 Å.H ydroxy and methoxy substituents are also nearly coplanar with the aromatic rings, except the O3 methoxy group, which twist to avoid steric hindrance with the neighbouring O2 and O4 methoxy groups, with the torsion of C16-O3-C12-C11 [99.6°]. Molecules are interlinked by the hydrogen bonds O-H···O with H···O distance of 1.89 Å,toform infinite zigzag chains parallel to the c axis. Fourthermore, C-H···p interactions interconnect zigzag chains into sheets perpendicular to the a axis, and make the adjacent sheets interact each other along a axis. Also, weak C-H···O bonds are co-responsible for the conformation of the crystal packing. C2-H2···O4 supports O-H···O and C14-H14···O1 supports C-H···p.H ydrogen bonds and C-H···p interactions assemble the molecules to three dimension networks.

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“…A number of hetercyclic resveratrol analogs have been reported and some of them have shown interesting biological activities [18][19][20][21][22]. However, for most of the reported analogs, the (E)-stilbene core structure is either maintained intact or only slightly modified.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and bioevaluation of novel heterostilbenes as potential anti-inflammatory and anti-angiogenic agents

Huang¹,

Lee²,

Shaw³

2013

MRI

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Novel heterocyclic analogs of resveratrol, (E)-stilbene analogs, were readily prepared by conjugation of a heterocyclic benzothiazolium moiety with the core styrene structure of resveratrol and evaluated for their biological properties. The results showed that these analogs were superior to resveratrol in 1) anti-angiogenesis in vitro, 2) nitric oxide inhibition in vitro, and 3) inhibition of carrageenan-induced edema in vivo. In summary, introduction of a heterocyclic benzothiazolium moiety to replace one of two aromatic rings from the core stilbene structure of resveratrol provided beneficial biological properties and is worthy of further investigation.

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A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts

Cited by 99 publications

References 48 publications

Resveratrol: A multitargeted agent for age-associated chronic diseases

Resveratrol: A multitargeted agent for age-associated chronic diseases

Crystal structure of (E)-1-(4-hydroxyphenyl)-2-(3,4,5-trimethoxyphenyl)- ethene, C17H18O4, a trans-stilbene

Synthesis and bioevaluation of novel heterostilbenes as potential anti-inflammatory and anti-angiogenic agents

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