Disease relevance of benzofuran

• The benzofuran structure is responsible for mitochondrial toxicity of amiodarone and the presence of iodine is not essential [1].
• We report a case of chronic active hepatitis caused by benzarone, a benzofuran derivative used in Europe for the treatment of peripheral venous disorders [2].
• While dioxetanes 1 and 2 were not mutagenic in Salmonella typhimurium strain TA100, benzofuran dioxetanes 3 exhibited substantial effects [3].
• Amiodarone, an iodinated benzofuran derivative, is used for treatment of refractory cardiac arrhythmias [4].
• Menthofuran (II, 4,5,6,7-tetrahydro-3,6-dimethyl benzofuran), the proximate toxin of R-(+)-pulegone (I), was administered orally to rats (200 mg/kg of body weight/day) for three days and the urinary metabolites were investigated [5].

Psychiatry related information on benzofuran

• Benzofuran derivatives as Abeta-aggregate-specific imaging agents for Alzheimer's disease [6].

High impact information on benzofuran

• Amiodarone, benzarone, and benzbromarone, but not benzofuran, also uncoupled oxidative phosphorylation [7].
• Irrespective of the death-inducing stimulus (glucocorticoids, topoisomerase inhibition, or Fas-crosslinking), a significant K+ outflow was observed during apoptosis, as determined on the single-cell level by means of the K+-sensitive fluorochrome, benzofuran isophtalate [8].
• The key step of the first route was facile cationic cyclization of the vinylogous benzofuran to the trisubstituted olefin (30 --> 16 + 38) to construct a six-membered carbocycle [9].
• In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models [10].
• The 6-methoxy- and 6-hydroxy-substituted benzofuran derivatives were shown to be potent CYP19 inhibitors (IC(50) = 0.01-1.46 microM) with activity greater than that observed for the unsubstituted parent compounds and inhibitory activity comparable with or greater than the reference compound arimidex (IC(50) = 0.6 microM) [11].

Chemical compound and disease context of benzofuran

• Amiodarone (Cordarone), a benzofuran derivative containing two atoms of iodine per molecule (37% of molecular weight), has recently been released in the United States for the management of refractory cardiac arrhythmias [12].
• Pseudomonas sp. 50432 biotransformed a highly toxic pesticide, carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) to 7-phenol (2,3-dihydro-2,2-dimethyl-7-hydroxy benzofuran) and several unknown metabolites [13].
• Modification of the C-2 position of a benzofuran derivative 6 (RO-09-4609), an N-myristoyltransferase (Nmt) inhibitor, has led us to discover antifungal agents that are active in a murine systemic candidiasis model [14].
• The benzofuran derivative carocainide is a new class I antiarrhythmic drug which has been shown to prevent and stop experimental ventricular arrhythmias [15].

Biological context of benzofuran

• Structure-activity relationship of antiestrogens: a study using triarylbutenone, benzofuran, and triarylfuran analogues as models for triarylethylenes and triarylpropenones [16].
• Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 2. Spiro-joined benzofuran, isobenzofuran, and benzopyran piperidines [17].
• Methylation, reduction of the double bond of the C(3)-side chain, reduction of the methoxycarbonyl functionalities to primary alcohols, or oxidation of the dihydrobenzofuran ring to a benzofuran system resulted in a decrease or loss of cytotoxic activity [18].
• Deuterium substitution of the methyl ether results in an inverse isotope effect on benzofuran hydroxylation (i.e. increased oxidation of this less favorable site) [19].
• This rapidly led to the 2',4'-difluorophenyl-dimethylamide 25 and the benzofuran 4 with high levels of potency (pK(i)) and good bioavailability in the rat and dog [20].

Anatomical context of benzofuran

• Mitochondrial K+ as modulator of Ca(2+)-dependent cytotoxicity in hepatocytes. Novel application of the K(+)-sensitive dye PBFI (K(+)-binding benzofuran isophthalate) to assess free mitochondrial K+ concentrations [21].
• PACAP-38 was able to induce a plasma membrane depolarization that was dependent on an influx of Na+ from the extracellular medium as confirmed by the monitoring of intracellular Na+ with the Na+-sensitive fluorescent dye sodium benzofuran isophtalate [22].
• The recently introduced K(+)-sensitive dye PBFI (K(+)-binding benzofuran isophthalate) has been used in combination with video-microscopy to assess intramitochondrial free K+ concentration ([K+]mito) in rat liver mitochondria in situ [21].
• Conversely, the dose-dependent inhibitory effect of amiodarone, an iodinated benzofuran derivative that antagonizes thyroid hormone actions, on INa was blocked when myocytes were pretreated with T3(100 n m, n=3), suggesting an interaction of T3 with amiodarone [23].
• These results demonstrate clearly that species differences in sensitivity to peroxisome proliferation with the benzofuran derivative do exist [24].

Associations of benzofuran with other chemical compounds

• We selected the benzo[b]thiophene and benzofuran combretastatin analogues 11 (ST2151) and 13 (ST2179) and their phosphate prodrugs (29 and 30) for their high antitumor activity in in vitro and in vivo models [25].
• Although, oral bioavailability was maintained when the indole molecular core was replace with the bioisosteric benzofuran or benzothiophene ring systems, it was found to not significantly impact the integrin activity or selectivity [26].
• The benzofuran (NTB), quinoxaline, and quinoline analogues (2, 3, and 4, respectively) were delta-selective opioid antagonists in vitro and bound selectively to delta receptors [27].
• This distortion is the result of strong hydrogen-bonding between the amide linker of the indole and benzofuran subunits, and the carbonyl of a central thymine base and second, weaker, hydrogen bond to the exocyclic NH(2) of the central guanine was also observed [28].
• Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER [29].

Gene context of benzofuran

• Development of dual-acting benzofurans for thromboxane A2 receptor antagonist and prostacyclin receptor agonist: synthesis, structure-activity relationship, and evaluation of benzofuran derivatives [30].
• These congeners, possessing the naphthyl, benzothiophene, benzyl, and benzofuran substituents, were predicted to satisfy the electrostatic requirements of the tryptophan binding pocket of SRIF [31].
• The benzofuran analogue 6i was administered in Sprague-Dawley rats and blocked the effects of an exogenous glucagon challenge [32].
• Models are presented for inhibition by benzofuran and benzothiophene biphenyl analogues of protein tyrosine phosphatase 1B (PTP1B), a target for insulin-resistant disease states [33].
• The OEL characteristics of the tert-butyl-substituted benzofuran trimer were explored, and blue emission was observed [34].

Analytical, diagnostic and therapeutic context of benzofuran

• The cytoplasmic concentration of Na+ ([Na+]i) was measured in individual mouse beta-cells using dual wavelength microfluorometry and the indicator sodium-binding benzofuran isophtalate [35].
• Neurons in neocortical brain slices were filled iontophoretically through an intracellular recording microelectrode with the Na+-sensitive dye benzofuran isophthalate (SBFI), and fluorescence images were recorded with a cooled charge-coupled device camera system using 380-nm illumination [36].
• The calcium- and potassium-sensitive dyes fura-2 and potassium-binding benzofuran isophtalate (PBFI) were used to study alterations in intracellular concentrations of calcium ([Ca(2+)](i)) and potassium ([K(+)](i)), respectively, while the perforated patch clamp technique was used to analyze transmembrane currents [37].
• The presence of potassium (K) in pollen, anthers and papillae from barley (Hordeum vulgare L.) flowers with different levels of developmental stages starting from boot stage to fully mature flower, was studied by using the K-sensitive fluorescent dye PBFI (potassium-binding benzofuran isophthalate) and confocal laser scanning microscopy [38].
• Following LH-20 and reverse phase HPLC chromatography, two compounds were isolated that had potent LTC4 inhibitory activity: medicarpin and 6-hydroxy-2-(2-hydroxy-4-methoxyphenyl) benzofuran (IV) with IC50s of 0.5 and 0.05 microM respectively [39].

References