benzofurans and conocarpan

Covering: 2000 to 2018 Natural products containing the 2,3-dihydrobenzofuran (2,3-DHB) skeleton have been the focus of a substantial number of synthetic studies since 2000. Herein, we review the total syntheses of decursivine, serotobenine, lithospermic acid, linderol A, bisabosqual A, pterocarpans, conocarpan, heliannuols, and some resveratrol oligomers, with emphasis on the synthetic strategies employed.

Topics: Benzofurans; Biological Products; Depsides; Heterocyclic Compounds, 4 or More Rings; Indole Alkaloids; Indoles; Molecular Structure

The present study determined the anti-Mycobacterium tuberculosis activities of supercritical CO2 extracts, neolignans eupomatenoid-5 (1), conocarpan (4) and eupomatenoid-3 (7) and their derivatives (2, 3, 5, 6, and 8) from Piper regnellii, as well as their cytotoxicities. The supercritical CO2 extract from leaves was purified by chromatographic methods, yielding compounds (1), (4) and (7), which were identified by (1)H NMR and comparison with literature data. Anti-M. tuberculosis activity (H37Rv and clinical isolates) was evaluated using a resazurin microtiter assay plate (REMA) to determine the MIC. The cytotoxicity assay was carried out in macrophages J774G.8 by sulforhodamine B colorimetric assay. The supercritical CO2 extracts from leaves and stems, and compound (4) showed activity against M. tuberculosis (MIC 15.6 μg/ml). Compound (1) showed the best activity (MIC 1.9 μg/ml), with good SI. Compounds (7) and (8) showed low activity against M. tuberculosis H37Rv. The derivative compounds did not show increased anti-M. tuberculosis activity. This is the first report, to our knowledge, to describe neolignans from P. regnellii with activity against M. tuberculosis, and compound (1) is a potential candidate for future antituberculosis drugs.

Topics: Animals; Antitubercular Agents; Benzofurans; Cell Line; Lignans; Macrophages; Magnetic Resonance Spectroscopy; Mice; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Phenols; Piper; Plant Extracts; Toxicity Tests

The antifungal activity of extracts obtained from Piper regnellii with supercritical carbon dioxide was tested against yeast and filamentous fungi. The most active extract was obtained from leaves extracts of P. regnellii at 40°C and 25 MPa, featuring a minimal inhibitory concentration of 3.9 μg/mL against Trichophyton mentagrophytes. Neolignans eupomatenoid-3, eupomatenoid-5, eupomatenoid-6 and conocarpan were present in all extracts. The results indicate the possibility of further studies on the use of extracts of P. regnellii obtained by supercritical extraction, as potential sources of bioactive compounds for use in medicine.

Topics: Antifungal Agents; Benzofurans; Chromatography, Supercritical Fluid; Microbial Sensitivity Tests; Phenols; Piper; Plant Extracts; Plant Leaves; Trichophyton

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID₅₀ 77 μg/cm²) as well compounds 1-11 (ID₅₀ 0.31-0.60 μmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID₅₀ 0.29 μmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E₂ synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Austria; Benzofurans; Cyclooxygenase 1; Edema; Intramolecular Oxidoreductases; Krameriaceae; Lignans; Male; Mice; NF-kappa B; Plant Roots; Prostaglandin-E Synthases

The antinociceptive properties of some fractions and two pure compounds, conocarpan and orientin, obtained from P. solmsianum leaves were investigated in several models of pain in mice. The results indicated that this plant exhibits a promising antinociceptive profile, as it produces active principles which are several times more active than some reference drugs used for comparison. The main compound tested, orientin, caused potent and dose-dependent effects against acetic acid-induced writhing and capsaicin- and glutamate-induced nociception, being more effective against the first one, with an ID(50) value of 6.5 mg/kg (14.5 micromol/kg). Orientin was about 20-fold more potent than acetylsalicylic acid and 3.5-fold more active than indomethacin. The antinociceptive effects of this plant may be attributed, at least partially, to the presence of conocarpan and, in particular, to the flavonoid orientin.

Topics: Analgesics; Animals; Benzofurans; Dose-Response Relationship, Drug; Flavonoids; Glucosides; Male; Mice; Pain; Pain Measurement; Piper; Piperaceae; Plant Extracts; Plant Leaves

Piperaceae is a family of tropical plants known to have antifungal, antibacterial, tumour-inhibitory, antiviral, antioxidant, molluscicidal and leishmanicidal activities. In this work, extracts and fractions from aerial parts of Piper abutiloides (Piperaceae), a traditional medicinal plant, were evaluated against the fungal species Candida albicans, C. parapsilosis, C. krusei, C. glabrata, C. tropicalis, Cryptococcus neoformans and Sporothrix schenckii. The results have shown that the antifungal activity of this plant can be concentrated in the hexanic fraction after partitioning its hydroalcoholic extract between hexane and 90% aqueous methanol. The chromatographic fractionation of the bioactive part was monitored with a bioautographic assay using C. glabrata, and allowed the isolation of three antifungal compounds: pseudodillapiol, eupomatenoid-6 and conocarpan. These compounds presented different potencies against the fungi tested, with the strongest effect being observed for eupomatenoid-6 against C. glabrata, which presented a minimal inhibitory concentration value of 0.3 microg spot(-1). Conocarpan showed antifungal activity without apparent cytotoxic effect on normal human lymphocytes, as assessed by the proliferation assay with human peripheral blood mononuclear cells stimulated with phytohaemaglutinin. This work reveals for the first time the occurrence of these compounds in P. abutiloides and justifies further studies to clarify their mechanisms of action.

Topics: Adult; Antifungal Agents; Benzofurans; Candida albicans; Chemical Fractionation; Chromatography; Cryptococcus neoformans; Female; Humans; Leukocytes, Mononuclear; Male; Microbial Sensitivity Tests; Phenols; Piper; Plant Extracts; Sporothrix; Young Adult

Catalytic asymmetric synthesis of neolignan natural products (-)-epi-conocarpan and (+)-conocarpan has been achieved by exploiting an enantio- and diastereoselective intramolecular C-H insertion reaction to construct a cis-2-aryl-2,3-dihydrobenzofuran ring system as a key step. The C-H insertion reaction of 5-bromoaryldiazoacetate catalyzed by Rh(2)(S-PTTEA)(4), a new dirhodium(II) carboxylate complex that incorporates N-phthaloyl-(S)-triethylalaninate as chiral bridging ligands, provided 2-aryl-5-bromo-3-methoxycarbonyl-2,3-dihydrobenzofuran with exceptionally high diastereoselectivity (cis/trans = 97:3) and high enantioselectivity for the cis isomer (84% ee).

Topics: Benzofurans; Catalysis; Lignans; Molecular Structure; Rhodium; Stereoisomerism

Two independent routes for the total synthesis of the bioactive neolignan (-)-conocarpan are described. The first (98% ee) is based on formal radical cyclization onto a benzene ring, and involves a 5-exo-trigonal closure onto a double bond restrained within a 6-membered ring. The second route (88% ee), which is shorter, is based on 5-exo-trigonal cyclization of an aryl radical onto a pendant terminal double bond. The two routes differ in their degree of stereoselectivity. The absolute configuration originally assigned to (+)-conocarpan had previously been called into question on the basis of empirical chiroptical rules; the present chemical work confirms the need for revision, and the assigned absolute configurations of several compounds correlated with (+)-conocarpan must also be changed.

Topics: Benzofurans; Cyclization; Free Radicals; Molecular Structure

(-)-Conocarpan (1) was synthesized by a method based on radical cyclization, and the absolute configuration was established by chemical degradation; the original 2R,3R-assignment to (+)-conocarpan should be reversed, as suggested by a later chiroptical study of model 2,3-dihydrobenzofurans.

Topics: Benzofurans; Cyclization; Furans; Molecular Conformation; Stereoisomerism

The antioxidant/photoprotective potential of a standardized Krameria triandra (KT) root extract (15% neolignans) has been evaluated in different cell models, rat erythrocytes and human keratinocytes cell lines, exposed to chemical (cumene hydroperoxide, CuOOH) and physical (UVB radiation) free radical inducers. The extract was significantly more active (IC50 0.28 +/- 0.04 microg/ml) than the typical chain-breaking antioxidant alpha-tocopherol (IC50 = 6.37 +/- 0.41 microg/ml) in inhibiting the CuOOH-induced hemolysis in rat blood cells. The KT constituent 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran, was the most active (IC50 = 0.03 +/- 0.005 microg/ml), followed by eupomatenoid 6 (IC50 = 0.29 +/- 0.06 microg/ml) and conocarpan (IC50 = 0.77 +/- 0.08 microg/ml). The same order of potency was observed in red blood cells exposed to UVB irradiation in continuo, with IC50 values 0.78 +/- 0.08 microg/ml for KT extract, 0.18 +/- 0.02 microg/ml for 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran, 0.95 +/- 0.11 microg/ml for eupomatenoid 6, and 3.8 +/- 0.39 microg/ml for conocarpan. In cultured human keratinocytes exposed to UVB radiation (50 mJ/cm2), KT extract (2.5-20 microg/ml) significantly and dose-dependently restrained the loss in cell viability and the intracellular oxidative damage: glutathione (GSH) depletion and the rise in dichlorofluorescein (DCF), marker of peroxide accumulation, were suppressed by 20 microg/ml KT and in parallel cell morphology maintained. The cytoprotective effect of the extract was confirmed in a more severe model of cell damage: exposure of keratinocytes to higher UVB doses (300 mJ/cm2), which induce a 50% cell death. In keratinocyte cultures supplemented with 10 microg/ml, cell viability was almost completely preserved and more efficiently than with (-)-epigallocatechin 3-gallate and green tea. The results of this study indicate the potential use of Rhatany extracts, standardized in neolignans, as topical antioxidants/radical scavengers against skin photodamage.

Topics: Animals; Antioxidants; Benzene Derivatives; Benzofurans; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Erythrocytes; Furans; Humans; Inhibitory Concentration 50; Keratinocytes; Lignans; Magnoliopsida; Male; Phenols; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Sunscreening Agents; Ultraviolet Rays

Activity-guided fractionation of the dichloromethane extract from leaves of Piper fulvescens, using an agar overlay bioautographic method, led to the isolation of three antifungal neolignans identified as conocarpan, eupomatenoid 5 and eupomatenoid 6. The minimal inhibitory concentration of these three neolignans against five fungi strains were determined. Conocarpan showed the widest activity, whereas eupomatenoid 6 was the most active against dermatophytes.

Topics: Antifungal Agents; Benzofurans; Candida albicans; Cryptococcus neoformans; Furans; Medicine, Traditional; Microbial Sensitivity Tests; Microsporum; Paraguay; Phenols; Piperaceae; Plant Extracts; Plant Leaves; Saccharomyces cerevisiae; Trichophyton

A new phenylcoumarone type trinorlignan, krametosan (1), along with the known norlignans, ratanhiaphenol I (2) and 2-(2'-hydroxy-4',6'-dimethoxyphenyl)-5-(E)-propenylbenzofuran (3), the lignan conocarpan (4) and dinorlignan decurrenal (5), were isolated from the CHCl3 extract of the roots of Krameria tomentosa. The structure of these compounds were elucidated by the spectroscopic methods.

Topics: Benzofurans; Brazil; Chromatography, Thin Layer; Furans; Lignans; Magnoliopsida; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Roots; Plants, Medicinal