Design, synthesis, and vasorelaxant and platelet antiaggregatory activities of coumarin–resveratrol hybrids

Vilar, Santiago; Quezada, Elías; Santana, Lourdes; Uriarte, Eugenio; Yáñez, Matilde; Fraiz, Nuria; Alcaide, Carlos; Cano, Ernesto; Orallo, Francisco

doi:10.1016/j.bmcl.2005.10.013

Cited by 143 publications

(33 citation statements)

References 14 publications

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“…Resveratrol has been reported to have a variety of pharmacological effects, including anti-inflammatory, anticarcinogenic, antioxidant, and antiplatelet properties (5,6,20,24,45,55,58). Several investigators have shown that resveratrol has both acute and chronic influences on organ systems (7,8,45,53) and endothelial function of large peripheral blood vessels during T1D (41,44).…”

mentioning

confidence: 99%

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

Arrick

Sun

Patel

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Arrick DM, Sun H, Patel KP, Mayhan WG. Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats. Am J Physiol Heart Circ Physiol 301: H696-H703, 2011. First published June 10, 2011; doi:10.1152/ajpheart.00312.2011.-Decreased dilation of cerebral arterioles via an increase in oxidative stress may be a contributing factor in the pathogenesis of diabetes-induced complications leading to cognitive dysfunction and/or stroke. Our goal was to determine whether resveratrol, a polyphenolic compound present in red wine, has a protective effect on cerebral arterioles during type 1 diabetes (T1D). We measured the responses of cerebral arterioles in untreated and resveratrol-treated (10 mg·kg Ϫ1 ·day Ϫ1 ) nondiabetic and diabetic rats to endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase (NOS)-dependent agonists and to a NOS-independent agonist. In addition, we harvested brain tissue from nondiabetic and diabetic rats to measure levels of superoxide under basal conditions. Furthermore, we used Western blot analysis to determine the protein expression of eNOS, nNOS, SOD-1, and SOD-2 in cerebral arterioles and/or brain tissue from untreated and resveratrol-treated nondiabetic and diabetic rats. We found that T1D impaired eNOS-and nNOSdependent reactivity of cerebral arterioles but did not alter NOSindependent vasodilation. While resveratrol did not alter responses in nondiabetic rats, resveratrol prevented T1D-induced impairment in eNOS-and nNOS-dependent vasodilation. In addition, superoxide levels were higher in brain tissue from diabetic rats and resveratrol reversed this increase. Furthermore, eNOS and nNOS protein were increased in diabetic rats and resveratrol produced a further increased eNOS and nNOS proteins. SOD-1 and SOD-2 proteins were not altered by T1D, but resveratrol treatment produced a decrease in SOD-2 protein. Our findings suggest that resveratrol restores vascular function and oxidative stress in T1D. We suggest that our findings may implicate an important therapeutic potential for resveratrol in treating T1D-induced cerebrovascular dysfunction.brain; N-methyl-D-aspartic acid; adenosine 5=-diphosphate; nitroglycerin; oxidative stress; superoxide CEREBRAL VASCULAR DISEASE leading to cognitive dysfunction and/or stroke is a complication of type 1 and type 2 diabetes. The risk of stroke is significantly higher in patients with diabetes than in persons without, and the mortality following a stroke is significantly higher in patients with diabetes compared with those without (4,25,37). Endothelial dysfunction appears to play an important role in the pathogenesis of vascular abnormalities during many disease states, including type 1 and type 2 diabetes (12,21,26,39,42). Many studies have shown that type 1 diabetes (T1D) affects endothelial cell function of large peripheral vessels by influencing the generation of nitric oxide via nitric oxide synthase (NOS) and/or via the formation of reactive oxygen species (11,23,36,38,40). In addition, we have sho...

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confidence: 99%

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

Arrick

Sun

Patel

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Two coumarins derivatives (30) and (31) have been reported to allow the relaxation of vascular smooth muscle and inhibiting platelet aggregation with a profle similar to that of trans-resveratrol (t-RESV) (32). Compound (31) is twice as high as that of t-resveratrol and a platelet antiaggregant activity that is six times higher [91]. More studies have been carried out to search for more effective chemical biological structures from natural plants.…”

Section: Anti-coagulant and Anti-plateletmentioning

confidence: 97%

The Structure and Pharmacological Functions of Coumarins and Their Derivatives

Wang²,

Xu³

et al. 2009

CMC

255

132

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Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, coumarins have attracted intense research interest. Of great interest is the possibility that this class of molecules could be a source of drugs for the therapy of several diseases. These include recent insights into inhibiting cell proliferation by interfering with mitotic spindle microtubule function, decrease Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M phases to interfere with processes of cell division, suppress O2(-) generation in leukocytes, inhibit different protein kinases, modulate the signalings, induce carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a mechanism inhibiting inflammation, progress in structure modification to increase in anti-fungal action, to broaden against bacteria spectrum, to enhance inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic side effects than the indanedione derivatives, they can be applied as an oral anticoagulant commonly for preventing venous thromboembolism following orthopedic surgery, recurrent myocardial infarction and the treatment of systemic embolism in atrial fibrillation, together with the significant advances in the basis of drug action. It is therefore useful to build up some correlations with the data available in order to better explore the molecular and cellular mechanism of coumarin action in the treatment of diseases. This review will focus on recent advances in molecular and cellular mechanisms of coumarin action involved with the relationship between structure and activity.

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“…It also found in fruits (e.g., bilberry, cloudberry), green tea and other foods such as chicory. Coumarin derivatives possess a remarkable range of biological properties including antioxidant [109,110], vasorelaxant [111], antiviral (92, 93) [112,113], anti-cancer (94, 95), and anti-inflammatory activities [114,115]. Lastly, suksdorfin (96), another natural compound isolated from the fruit of Lomatium suksdorfii, exhibits a significant anti-HIV activity as it inhibits the viral replication in the T-cell line with an EC 50 in the 2.5 µM range [116] (Figure 8).…”

Section: Benzopyrones: Coumarins and Chromonesmentioning

confidence: 99%

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

et al. 2016

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This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed.

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Design, synthesis, and vasorelaxant and platelet antiaggregatory activities of coumarin–resveratrol hybrids

Cited by 143 publications

References 14 publications

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

The Structure and Pharmacological Functions of Coumarins and Their Derivatives

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

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