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Dual peroxisome proliferator-activated receptor-α/γ (PPARα/γ) agonists regulate both lipid and glucose homeostasis under different metabolic conditions and can exert anti-inflammatory activity. We investigated the potential dual PPARα/γ agonism of prenylated benzopyrans polycerasoidol (1) and polycerasoidin (2) and their derivatives for novel drug development. Nine semisynthetic derivatives were prepared from the natural polycerasoidol (1) and polycerasoidin (2), which were evaluated for PPARα, -γ, -δ and retinoid X receptor-α activity in transactivation assays. Polycerasoidol (1) exhibited potent dual PPARα/γ agonism and low cytotoxicity. Structure–activity relationship studies revealed that a free phenol group at C-6 and a carboxylic acid at C-9′ were key features for dual PPARα/γ agonism activity. Molecular modeling indicated the relevance of these groups for optimal ligand binding to the PPARα and PPARγ domains. In addition, polycerasoidol (1) exhibited a potent anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium in a concentration-dependent manner via RXRα/PPARγ interactions. Therefore, polycerasoidol (1) can be considered a hit-to-lead molecule for the further development of novel dual PPARα/γ agonists capable of preventing cardiovascular events associated with metabolic disorders.

Abstract The aims of the present study were to analyse the effects of an oral daily dose (10 mg/kg) of the dietary flavonoid quercetin for five weeks in two-kidney, one-clip (2K1C) Goldblatt (GB) hypertensive rats. The evolution of systolic blood pressure was followed by weekly measurements, and morphological variables, proteinuria, plasma nitrates plus nitrites (NOx) and thiobarbituric acid reactive substances (TBARS), liver oxidative stress markers and endothelial function were determined at the end of the experimental period. Quercetin treatment reduced systolic blood pressure of GB rats, producing no effect in control animals. It also reduced cardiac hypertrophy and proteinuria developed in GB hypertensive rats. Decreased endothelium-dependent relaxation to acetylcholine of aortic rings from GB rats was improved by chronic quercetin treatment, as well as increased endothelium-dependent vasoconstrictor response to acetylcholine and overproduction of TXB2 by aortic vessels of GB rats, being without effect in normotensive animals. Increased plasma NOx and TBARS, and decreased liver total glutathione (GSH) levels and glutathione peroxidase (GPX) activity were observed in GB hypertensive rats compared to the control animals. Normalisation of plasma NOx and TBARS concentrations and improvement of the antioxidant defences system in liver accompanied the antihypertensive effect of quercetin. We conclude that chronic oral treatment with quercetin shows both antihypertensive and antioxidant effects in this model of renovascular hypertension. (Mol Cell Biochem 270: 147–155, 2005)

Covering: the literature from 1998 to 2004

Thirty‐one bioactive styryl‐lactones, with six different basic skeletons, have been isolated from Goniothalamusspecies. Aspects of their isolation, structural elucidation, biogenesis and biological activity are reviewed. Copyright © 1999 John Wiley & Sons, Ltd.

Thirty-one bioactive styryl-lactones, with six different basic skeletons, have been isolated from Goniothalamus species. Aspects of their isolation, structural elucidation, biogenesis and biological activity are reviewed. Copyright © 1999 John Wiley & Sons, Ltd.

The fractionation of the methanolic extract of Goniothalamus arvensis (Annonaceae) stem bark led to the isolation of two novel styryl-lactones, arvensin and (+)-2-epi-altholactone. The structures of these compounds, which belong to the furano-pyrone group, were established on the basis of mass spectrometry, one- and two-dimensional nuclear magnetic resonance experiments, as well as simple chemical derivatization. The relative and absolute configurations of the compounds are discussed. Copyright © 1999 John Wiley & Sons, Ltd.

The fractionation of the methanolic extract of Goniothalamus arvensis(Annonaceae) stem bark led to the isolation of two novel styryl‐lactones, arvensin and (+)‐2‐epi‐altholactone. The structures of these compounds, which belong to the furano‐pyrone group, were established on the basis of mass spectrometry, one‐ and two‐dimensional nuclear magnetic resonance experiments, as well as simple chemical derivatization. The relative and absolute configurations of the compounds are discussed. Copyright © 1999 John Wiley & Sons, Ltd.

The fractionation of the MeOH extract from the stem bark of Goniothalamus arvensis (Annonaceae) led to the isolation of a new styryl-lactone, (+)-goniotharvensin (1), and two other known styryl-lactones: (+)-altholactone (2) and (+)-isoaltholactone (3). Goniotharvensin (1), is a tetrahydrofurano-5-pyrone whose structure was established on the basis of MS and NMR experiments as well as chemical derivatization.

Two benzylisoquinoline and four aporphine alkaloids were isolated from roots of an oceanic Annonaceae, Xylopia papuana. The benzylisoquinoline alkaloids displayed a selectivity for dopamine receptors whereas aporphine alkaloids, specially anonaine, inhibited selectively dopamine uptake.

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.