Clementina M. M. Santos

2-Styrylchromones As Novel Inhibitors of Xanthine Oxidase. A Structure-activity Study

The purpose of this study was the evaluation of the xanthine oxidase (XO) inhibition produced by some synthetic 2-styrylchromones. Ten polyhydroxylated derivatives with several substitution patterns were synthesised, and these and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation of uric acid from xanthine. The synthesised 2-styrylchromones inhibited xanthine oxidase in a concentration-dependent and non-competitive manner. Some IC 50 values found were as low as 0.55 μM, which, by comparison with the IC 50 found for allopurinol (5.43 μM), indicates promising new inhibitors. Those 2-styrylchromones found to be potent XO inhibitors should be further evaluated as potential agents for the treatment of pathologies related to the enzymes activity, as is the case of gout, ischaemia/reperfusion damage, hypertension, hepatitis and cancer.

2,3-diarylxanthones as strong scavengers of reactive oxygen and nitrogen species: a structure-activity relationship study.

Xanthones are a class of oxygen-containing heterocyclic compounds widely distributed in nature. The natural derivatives can present different substitutions in the xanthone core that include hydroxyl, methoxyl, prenyl and glycosyl groups. The inclusion of aryl groups has only been reported for a few synthetic derivatives, the 2,3-diaryl moiety being recently introduced by our group. Xanthones are endowed with a broad spectrum of biological activities, many of them related to their antioxidant ability, including the scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as metal chelating effects. Considering the interesting and promising antioxidant activities present in compounds derived from the xanthone core, the main goal of this work was to evaluate the scavenging activity of the new 2,3-diarylxanthones for ROS, including superoxide radical (O2-), hydrogen peroxide (H2O2), singlet oxygen (1O2), peroxyl radical (ROO.) and hypochlorous acid (HOCl), and RNS, including nitric oxide (.NO) and peroxynitrite anion (ONOO-). The obtained results revealed that the tested 2,3-diarylxanthones are endowed with outstanding ROS and RNS scavenging properties, considering the nanomolar to micromolar range of the IC50 values found. The xanthones with two catechol rings were the most potent scavengers of all tested ROS and RNS. In conclusion, the new 2,3-diarylxanthones are promising molecules to be used for their potential antioxidant properties.

Chalcones as Versatile Synthons for the Synthesis of 5- and 6-membered Nitrogen Heterocycles

Chalcones belong to the flavonoid family which constitutes one of the major classes of naturally occurring oxygen heterocyclic compounds. The , -unsaturated carbonyl system of chalcones possesses two electrophilic reactive centers allowing them to participate in addition reactions via attack to the carbonyl group (1,2-addition) or involving the -carbon (1,4-conjugate addition), leading to the synthesis of promising bioactive heterocyclic compounds. The purpose of this review is to present a systematic survey of the most recent literature that uses chalcones in the synthesis of biologically active 5and 6-membered nitrogen heterocycles such as pyrroles, indoles, isoxazoles, imidazoles, pyrazoles, indazoles, triazoles, tetrazoles, pyridines and pyrimidines. Efficiency, easy-to-handle and cheap reagents, alternative heating conditions and greener protocols will be highlighted. In this review we will cover the literature since the beginning of the 21 century in more than 400 publications.

Novel chromone and xanthone derivatives: Synthesis and ROS/RNS scavenging activities

Chromones and xanthones are oxygen-containing heterocyclic compounds acknowledged by their antioxidant properties. In an effort to develop novel agents with improved activity, a series of compounds belonging to these chemical classes were prepared. Their syntheses involve the condensation of appropriate 2-methyl-4H-chromen-4-ones, obtained via Baker-Venkataraman rearrangement, with (E)-3-(3,4-dimethoxyphenyl)acrylaldehyde to provide the corresponding 2-[(1E,3E)-4-(3,4-dimethoxyphenyl)buta-1,3-dien-1-yl]-4H-chromen-4-ones. Subsequent electrocyclization and oxidation of these compounds led to the synthesis of 1-aryl-9H-xanthen-9-ones. After cleavage of the protecting groups, hydroxylated chromones and xanthones were assessed as scavenging agents against both reactive oxygen species (ROS) [superoxide radical (O2(•-)), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen ((1)O2), and peroxyl radical (ROO(•))] and reactive nitrogen species (RNS) [nitric oxide ((•)NO) and peroxynitrite anion (ONOO(-))]. Generally, all the tested new hydroxylated chromones and xanthones exhibited scavenger effects dependent on the concentration, with IC50 values found in the micromolar range. Some of them were shown to have improved scavenging activity when compared with previously reported analogues, allowing the inference of preliminary conclusions on the structure-activity relationship.

Synthesis and Transformation of Halochromones

Natural and synthetic chromone derivatives have been assigned as lead structures in drug development with some already being marketed [3]. The majority of the naturally occurring chromones are 2and 3-aryl derivatives, called flavones 1b and isoflavones 1c, respectively. However, other types of chromones have also been found in the plant kingdom, such as 3-methylchromones 1d and 2styrylchromones 1e (Fig. 1).

Six-Membered Ring Systems: With O and/or S Atoms

Abstract The review covers work published in the calendar year 2011. Novel reaction chemistry and new ring synthetic methods for pyrans, [1]benzopyrans, dihydro[1]benzopyrans (chromenes, chromans), [2]benzopyrans, dihydro[2]benzopyrans (isochromenes, isochromans), pyranones, coumarins, chromones, xanthenes, xanthones, thiopyrans, dioxins, dioxanes, trioxanes, tetraoxanes, dithianes, trithianes, and oxathianes are reviewed.

Arylxanthones and arylacridones: a synthetic overview

Abstract Arylxanthones and arylacridones although not yet found in nature are becoming an important group of heterocyclic compounds due to their promising biological activities. Their central cores, xanthone and acridone, are recognized as interesting motifs for drug development mainly to be used in antitumour chemotherapy. The synthesis of this type of compounds is still scarce but several successful examples were recently published and a large variety of arylated xanthone and acridone derivatives were prepared. A systematic survey of the literature dedicated to their synthesis will be presented and discussed in this review.

Synthesis of Chromone-Related Pyrazole Compounds

Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both chromone and pyrazole rings. The methods reviewed include the synthesis of chromone-pyrazole dyads, synthesis of chromone-pyrazole-fused compounds, and chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the chromone and pyrazole dual chemistry and their outcomes in the 21st century.

Dimethyldioxirane Oxidation of Exocyclic (E,E)-Cinnamylideneketones

Exocyclic (E,E)-cinnamylideneketones were oxidized by an excess of isolated dimethyldioxirane (DMDO, in acetone solution) at room temperature, providing diastereomeric mixtures of the α,β:γ,δ-diepoxides. In the case of derivatives bearing an ortho-nitrocinnamylidene moiety, α,β-monoepoxides were also isolated as minor products. The structures of all new compounds and the stereochemistry of the monoepoxides and diepoxide diastereomers were established by NMR studies.

First intramolecular Diels–Alder reactions using chromone derivatives: synthesis of chromeno[3,4-b]xanthones and 2-(benzo[c]chromenyl)chromones

A series of novel (E)-2-(2-propargyloxystyryl)chromones and (E,E)-2-[4-(2-propargyloxyphenyl)buta-1,3-dien-1-yl]chromones were designed and synthesized via aldol condensation of 2-methylchromones with 2-propargyloxy(benzaldehyde and cinnamaldehyde), respectively. Both chromone derivatives were used as substrates in microwave-assisted intramolecular Diels–Alder reactions, affording chromeno[3,4-b]xanthones and 2-(benzo[c]chromenyl)chromones. This is the first report involving chromone derivatives in intramolecular Diels–Alder reactions for the synthesis of new oxygen heterocycles, namely xanthone- and flavone-type compounds.