Bisabolane Sesquiterpenes Research Articles

Antiparasitic Compounds from Cupania cinerea with Activities against Plasmodium falciparum and Trypanosoma bruceirhodesiense

In a survey of plants from Ecuador with antiprotozoal activity, Cupania cinerea was found to show significant in vitro activity against the Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense. Subsequently, activity-guided isolation of the n-hexane and dichloromethane extracts from the bark of C. cinerea afforded two diterpene glycosides (1 and 2), named cupacinoside and 6'-de-O-acetylcupacinoside, and a lactonized triterpene bearing an oxepin moiety named cupacinoxepin (3), together with the known compounds scopoletin (4), caryophyllene oxide (5), two bisabolane sesquiterpenes (6 and 7), lichexanthone (8), gustastatin (9), lupenone (10), betulone (11), 17β,21β-epoxyhopan-3-one (12), taraxerol (13), and taraxerone (14). For compound 3, X-ray crystallography was employed to elucidate the relative configuration. For cupacinosides (1) and (2) and cupacinoxepin (3), in vitro activities against the P. falciparum K1 strain (IC(50)1, 1.3; 2, 1.8; and 3, 8.7 μM) and T. b. rhodesiense (IC(50)1, 4.5; 2, 15.8; and 3, 71.6 μM) were found. Cytotoxicity toward L-6 cells is discussed for all the compounds isolated.

Facile Total Synthesis of Xanthorrhizol

A facile total synthesis of the bisabolane sesquiterpene, xanthorrhizol (1), has been achieved in 6 steps, in 48% overall yield. The starting material was 3-methoxy-4-methyl-phenoacetone (7), and a Claisen-Johnson rearrangement was used as the key step to construct the skeleton of the target molecule.

Efficient Total Synthesis of Racemic Bisabolane Sesquiterpenes Curcuphenol and Xanthorrhizol Starting from Substituted Acetophenones

AbstractA total synthesis of natural bisabolane sesquiterpenes curcuphenol (1) and xanthorrhizol (2) was developed by using the substituted acetophenones 4 and 5, respectively, as starting materials. The acetyl group of the latter was activated through ethoxycarbonylation to carry out the prenylation, which was performed successfully to give their respective precursors 11a and 11b, and 21 that were converted into the corresponding natural sesquiterpenes 1 and 2, respectively, over four steps and in high overall yields.

Synthesis of bisabolane sesquiterpenes: A Johnson-Claisen rearrangement approach

Abstracts Several bisabolane sesquiterpenes, (±)-curcumene, (±)-curcuphenol, (±)-curcudiol and (±)-curcuhydroquinone, have been synthesized in racemic form and fully characterized. The salient characteristic of our approach is that a Johnson-Claisen arrangement was involved as a key step.

A new Bisabolane Derivative of Leontopodium andersonii

Phytochemical investigations of the roots of Leontopodium andersonii C. B. Clarke (Asteraceae) resulted in the isolation of a new bisabolane sesquiterpene derivative. The structure of the highly substituted derivative (1R*,5S*,6S*)-5-(acetyloxy)-6-[3-(acetyloxy)-1,5-dimethylhex-4-enyl]-3-methylcyclohex-2-en-4-on-1-yl(2Z)-2-methyl-but-2-enoate was established by 1- and 2-D-NMR spectroscopy and is the first report of a bisabolone derivative of the genus Leontopodium.

Altaicalarins A-D, cytotoxic bisabolane sesquiterpenes from Ligularia altaica.

Four new bisabolane sesquiterpenes, altaicalarins A-D (1-4), and three known analogues (5-7) were isolated from the roots and rhizomes of Ligularia altaica. The structures were elucidated by spectroscopic methods including 2D NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. The isolated compounds were also evaluated for cytotoxic activity against human lung carcinoma (A-549), human breast adenocarcinoma (MCF-7), epidermoid carcinoma of the nasopharynx (KB), and vincristine-resistant nasopharyngeal (KBVIN) cell lines, and 1 was found to show significant cytotoxicity, with EC(50) values of 3.4, 0.8, 1.0, and 0.9 microg/mL, respectively.

LC–UV Assay for Simultaneous Estimation of Aromatic Turmerone, α/β-Turmerone and Curlone: Major Bisabolane Sesquiterpenes of Turmeric Oil in Rabbit Plasma for Application to Pharmacokinetic Studies

The herbal medicament derived from the lipid soluble fraction obtained from Curcuma longa L. (Zingiberaceae) has shown potential neuroprotective activity in disorders like stroke. HM has been standardized with three biomarkers: ar-turmerone, α/β-turmerone and curlone, major bisabolane sesquiterpenes of turmeric oil. Development of a biaonalytical method for these sesquiterpenes was initiated to characterize its preclinical pharmacokinetics in rabbits to accelerate its development as a potential candidate for vascular complications. Since, the compounds are structurally and chemically very similar, gradient elution was utilized on a C-18 reversed phase column with a mobile phase comprising of acetonitrile and deionised water. The UV detector was set at wavelengths 240 and 270 nm. The sample clean-up was performed by protein precipitation with acetonitrile. The method was reasonably sensitive with limits of quantitation (LOQ) of 0.098 μg mL−1 in plasma for all the analytes. Accuracy and precision were within the acceptable limits, as indicated by relative standard deviation (% RSD) varying from 1.3 to 13.6% and bias values ranging from −5.5 to 10.3%, respectively. Moreover, the analytes were stable in plasma even after three freeze-thaw cycles. The method was applied to generate preliminary pharmacokinetics of turmeric oil in rabbits after intravenous administration.

The Bisabolane Sesquiterpenoid Endoperoxide, 3,6-Epidioxy-1,10-bisaboladiene, Isolated fromCacalia delphiniifoliaInhibits the Growth of Human Cancer Cells and Induces Apoptosis

In the course of our screening for a new anti-tumor substance, the bisabolane sesquiterpenoid endoperoxide, 3,6-epidioxy-1,10-bisaboladiene (EDBD), was isolated from the edible wild-plant, Cacalia delphiniifolia. EDBD showed cytotoxicity toward human chronic myelogenous leukemia K562 and human prostate carcinoma LNCaP cell lines with IC50 values of 9.1 microM and 23.4 microM, respectively. DNA fragmentation and condensation of chromatin, the hallmarks of apoptosis, appeared in K562 cells after an 18-h treatment with EDBD. alpha-Curcumene, a bisabolane sesquiterpene that lacks the endoperoxide moiety of EDBD, also showed cytotoxicity toward both K562 and LNCaP cell lines at over a 10-times higher dose than that of EDBD. The results indicate the importance of the endoperoxide structure within EDBD to its anti-tumor activity in vitro.

Pyrrolizidine Alkaloids and Bisabolane Sesquiterpenes from the Roots of Ligularia cymbulifera

AbstractThe new pyrrolizidine alkaloid glycoside 1, and the three new highly oxygenated bisabolane sesquiterpenes 4–6, together with the two known pyrrolizidine alkaloids 2 and 3, were isolated from the roots of Ligularia cymbulifera (W. W. Smith) Hand.‐Mazz. Their structures were established on the basis of spectroscopic analysis, especially 1D‐ and 2D‐NMR data. The cytotoxic activities of compounds 1, 2, and 4–6 were evaluated against hepatoma (BEL‐7402), human leukemia (HL‐60), human ovarian carcinoma (HO‐8910), and nasopharyngeal carcinoma (KB) cell lines (Tables 1–3). Compound 6 showed weak cell‐growth inhibition of BEL‐7402 cell.

New Bisabolane Sesquiterpenes and Coumarin from Leontopodium longifolium

From the roots of Leontopotium longifolium, three new bisabolane sesquiterpenes, rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-1,5-dimethylhexa-3,5-dienyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (1), rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (2), rel-(1R,2S,4R,5S)-4-acetoxy-2-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-5-methylcyclohexyl (Z)-2-methylbut-2-enoate (3), and a new coumarin, 2,3-dihydro-5-hydroxy-2-(1-methylethenyl)-7H-pyrano[2,3-g][1,4]benzodioxin-7-one (4) together with nine known compounds have been isolated. The structures of these compounds were established by spectroscopic methods. Compounds 1 and 2 exhibited moderate cytotoxic activities against human promyelocytic leukemia (HL-60) cells.

Bisabolane Sesquiterpenes from the Roots of Ligularia cymbulifera

Eight new highly oxygenated bisabolane sesquiterpenes (1-8), of which one contains a chlorine atom, were obtained in a phytochemical investigation of the roots of Ligularia cymbulifera, and their structures were elucidated by interpretation of spectroscopic data. Their relative configurations were clarified by a detailed analysis of (1)H NMR coupling constants and by NOE experiments. Compounds 1-8 were evaluated for antimicrobial activity against three bacterial cultures and a yeast culture.

The Enantioselective Syntheses of Bisabolane Sesquiterpenes Lepistirone and Cheimonophyllon E.

Abstract The synthetic approach to the bisabolane sesquiterpenes Lepistirone 1 and Cheimonophyllon E 2 involves the transformation of (+)-2-carene ( 5 ) into the p -menthane furans 8 and 11 . Regio- and stereoselective alkylation, and standard reactions complete the enantioselective syntheses.

Composition of the essential oil of the liverwort Radula perrottetii of Japanese origin

Analysis of the essential oil of the liverwort Radula perrottetii afforded two novel viscidane diterpenes, viscida-3,9,14-triene ( 1), viscida-3,11(18),14-triene ( 2), four bisabolane sesquiterpenes, bisabola-2,6,11-triene ( 3), bisabola-1,3,5,7(14),11-pentaene ( 4), bisabola-1,3,5,7,11-pentaene ( 5), 6,7-epoxybisabola-2,11-diene ( 6), and 1-methoxy-4-(2-methylpropenyl)benzene ( 7) as new natural products. In addition, the known compounds bisabola-1,3,5,7(14),10-pentaene ( 8), ar-tenuifolene ( 9), α-helmiscapene ( 10), and β-helmiscapene ( 11) were also isolated. Isolation was carried out by preparative gas chromatography, and the structures were established by extensive NMR analysis. This is the first finding of viscidane diterpenes in liverworts. Compounds 8, 9 and the rarely encountered eudesmane sesquiterpene hydrocarbons 10 and 11 are reported for the first time from R. perrottetii.

The enantioselective syntheses of bisabolane sesquiterpenes Lepistirone and Cheimonophyllon E

The synthetic approach to the bisabolane sesquiterpenes Lepistirone 1 and Cheimonophyllon E 2 involves the transformation of (+)-2-carene ( 5 ) into the p-menthane furans 8 and 11 . Regio- and stereoselective alkylation, and standard reactions complete the enantioselective syntheses.

Novel sesquiterpenoid matrix metalloproteinase-3 inhibitors from an acid mine waste extremophile.

Berkeley Pit Lake is a 1500 ft deep abandoned open-pit copper mine filled with 30 billion gallons of acidic, metal-contaminated water. This harsh environment is proving to be a source of unusual, biologically active microorganisms. Bioassay-guided fractionation using signal transduction enzyme assays led to the isolation of three novel bisabolane sesquiterpenes and a novel coumarin. The isolation and characterization of these compounds are reported here.

Anti-inflammatory activity of Leontopodium alpinum and its constituents.

The aerial parts and roots of Leontopodium alpinum Cass. (Asteraceae) were investigated for their in vivo topical anti-inflammatory activity using the inhibition of Croton oil-induced ear dermatitis in mice. For both of the plant parts, the dichloromethane extract induced a dose-dependent oedema reduction, being more active than the methanol and 70% aqueous methanol ex-tracts. Moreover, the dichloromethane extract of the aerial parts was more active than that of the roots (ID50 = 221 and 338 pg/cm2, respectively). Fatty acids make a significant contribution to the anti-oedema activity of the dichloromethane extract of the aerial parts, whereas bisabolane sesquiterpenes, tricyclic sesquiterpenes, coumarins and lignans are involved in the activity of the root extract. Two bisabolane derivatives reduced also the polymorphonuclear neutrophil leukocytes accumulation in the inflamed tissue, while a 7a-silphiperfol-5-ene type sesquiterpene and a coumarin derivative inhibited the in vitro chemotaxis of these inflammatory cells.

A New Cytotoxic Tetralone Derivative from Humicola grisea, a Filamentous Fungus from Wood in the Southeastern Lagoon of New Caledonia

AbstractFor Abstract see ChemInform Abstract in Full Text.

Antifungal constituents of the stem bark of Bridelia retusa

Antifungal activity guided fractionation of solvent extracts of the stem bark of Bridelia retusa of the family Euphorbiaceae against Cladosporium cladosporioides, furnished new bisabolane sesquiterpenes, ( E)-4-(1,5-dimethyl-3-oxo-1-hexenyl)benzoic acid, ( E)-4-(1,5-dimethyl-3-oxo-1,4-hexadienyl) benzoic acid, ( R)-4-(1,5-dimethyl-3-oxo-4-hexenyl)benzoic acid and (−)-isochaminic acid, together with the known ( R)-4-(1,5-dimethyl-3-oxohexyl)benzoic acid (ar-todomatuic acid), 5-allyl-1,2,3-trimethoxybenzene (elemicin), (+)-sesamin and 4-isopropylbenzoic acid (cumic acid). All these compounds showed fungicidal activity on TLC bioautography method at very low concentrations except elemicin.

A new cytotoxic tetralone derivative from Humicola grisea, a filamentous fungus from wood in the southeastern lagoon of New Caledonia

Humicolone, a new phenolic tetralone in acetal form, was isolated, together with a known phenolic tetralone, from cultures of Humicola grisea Traaen, a hyphomycete taken from drifting wood in the southeastern lagoon of New Caledonia. Humicolone, determined from MTPA esters to have absolute configuration 1′ R,3 S,4 S, showed cytotoxicity on KB cell lines, with IC 50 values between 1 and 5 ppm. Another unidentified filamentous fungus, also from drifting wood in a nearby New Caledonian marine area, gave phosphatidyl cholines and, unusually for fungi, a bisabolane sesquiterpene.

Assignment of the 1H and 13C NMR Spectra of a New Antibacterial Bisabolane Sesquiterpene by Two-Dimensional NMR Techniques

A new antibacterial bisabolane sesquiterpene, 1β-acetoxy-2β,8-diangeloyloxy-3β-hydroxy-4α-cbioro-10,11-expoxybisabol-7(14)-ene (1), was isolated from Ligularia thyrsoidea and its structure was elucidated by 2D NMR techniques.