ABSTRACT
Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5-dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in vitro growth inhibitory activity that ranged between the activities of etoposide and carboplatin, chosen as reference compounds, in six distinct cancer cell lines. Compound 1 displayed less activity than 2. Computer-assisted phase-contrast microscopy-related analysis revealed that 2 displayed cytostatic, not cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis further confirmed that 2 does not induce apoptotic features in U373 or A549 cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived.
Subject(s)
Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cytostatic Agents/isolation & purification , Neosartorya/chemistry , Antineoplastic Agents/chemistry , Apoptosis , Carcinoma, Non-Small-Cell Lung/pathology , Cytostatic Agents/chemistry , Cytostatic Agents/pharmacology , Dioxoles/isolation & purification , Dioxoles/pharmacology , Drug Screening Assays, Antitumor , Glioblastoma/pathology , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Magnetic Resonance Spectroscopy , Microscopy, Phase-Contrast/methods , Mitosis/drug effects , Neosartorya/growth & development , Neosartorya/isolation & purification , Pyrazines/isolation & purification , Pyrazines/pharmacology , Pyridines/isolation & purification , Pyridines/pharmacology , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Soil MicrobiologyABSTRACT
Chemical investigation of a collection of the fungus Neosartorya glabra from Thailand furnished sartoryglabins A-C (1a, 1b and 2) which are analogs of the reverse prenylated indole alkaloids known as (-) ardeemins. Structures of these compounds were established by NMR spectrometry and an X-ray analysis. Sartoryglabins A-C were evaluated for their in vitro growth inhibitory activity on three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma). All the compounds exhibited strong to moderate activity against the MCF-7 cell line but weak or no activity against the NCI-H460 and A375-C5 cell lines. Sartoryglabin B was found to exhibit selectivity towards the MCF-7 cell line.
Subject(s)
Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Neosartorya/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Humans , Models, Molecular , Molecular StructureABSTRACT
An ethanol extract of the aerial parts of Delphinium gracile DC. yielded five flavonol glycosides quercetin-3-O-{[beta-d-xylopyranosyl (1-->3)-4-O-(E-p-caffeoyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranosyl (1-->2)]}-beta-d-glucopyranoside (1), quercetin-3-O-{[beta-d-xylopyranosyl (1-->3)-4-O-(E-p-coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranosyl (1-->2)]}-beta-d-glucopyranoside (2), quercetin-3-O-{[beta-d-xylopyranosyl (1-->3)-4-O-(Z-p-coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranosyl (1-->2)]}-beta-d-glucopyranoside (3), kaempferol-3-O-{[beta-d-glucopyranosyl (1-->3)-4-O-(E-p-coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranoside-7-O-(4-O-acetyl)-alpha-l-rhamnopyranoside (4) kaempferol-3-O-{[beta-d-glucopyranosyl (1-->3)-4-O-(E-p-coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranoside-7-O-(4-O-acetyl)-alpha-l-rhamnopyranoside (5) in addition to 4-(beta-d-glucopyranosyloxy)-6-methyl-2H-pyran-2-one (6) and rutin. Structures were elucidated by spectroscopic methods.
Subject(s)
Delphinium/chemistry , Flavonols/chemistry , Glycosides/chemistry , Glycosides/isolation & purification , Acylation , Magnetic Resonance SpectroscopyABSTRACT
One new prenylated xanthone 5-farnesyltoxyloxanthone B ( 4), three known xanthones alpha-mangostin ( 1), rubraxanthone ( 2) and isocowanol ( 3) as well as (2 E,6 E,10 E)-4beta-hydroxy-3-methyl-5beta-(3,7,11,15-tetramethylhexadeca-2,6,10-tetraenyl)-cyclohex-2-en-1-one ( 5) and 3,3',4- O-trimethylellagic acid were isolated from the wood of GARCINIA MERGUENSIS Wight. The cytotoxic activities of compounds 1 - 5 were evaluated against the MCF-7, MDA-MB-231, NCI-H-460 and SF-268 cell lines with rubraxanthone 2 and 5 exhibiting the highest activity at 9.0 and 12.1 microM, respectively, against MCF-7 cells.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Garcinia/chemistry , Wood/chemistry , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Xanthones/chemistryABSTRACT
The flavonoids kaempferol, quercetin, trifolin, hyperoside 2''- and 6''- acetates, 7-glucotrifolin, biorobin and robinin were isolated from the aerial parts of Consolida oliveriana. Their derivatives kaempferol tetraacetate, quercetin pentaacetate, trifolin heptaacetate and hyperoside octaacetate exhibited significant cytotoxicity IN VITRO against three human cell lines HL-60, U937 and SK-MEL-1 while hyperoside 2''-acetate, hyperoside-6''-acetate, glucotrifolin decaacetate and heptamethyltrifolin were inactive.
Subject(s)
Cell Survival/drug effects , Flavonoids/pharmacology , Galactosides/pharmacology , Glycosides/pharmacology , Kaempferols/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Ranunculaceae/chemistry , Cell Division/drug effects , Cell Line, Tumor , HL-60 Cells/drug effects , Humans , MethylationABSTRACT
Chemical study of a previously undescribed fungus, Talaromyces thailandiasis, furnished the two new merodrimanes thailandolides A (1) and B (2), an O-methylated derivative (3) of the aromatic fragment incorporated in thailandolide B, and three known closely related 1(3H)-isobenzofuran derivatives, penisimplicissin (4a), vermistatin (4b), and hydroxydihydrovermistatin (4c). Structures were established by spectroscopic measurements and confirmed by X-ray analyses of compounds 1 and 4b. The unusual peptide analogue N-benzoylphenylalanyl-N-benzoylphenyl alaninate (5) isolated earlier from a higher plant was also found.
Subject(s)
Sesquiterpenes/isolation & purification , Talaromyces/chemistry , Crystallography, X-Ray , Molecular Conformation , Molecular Structure , Sesquiterpenes/chemistry , ThailandABSTRACT
The pyridoacridine alkaloids kuanoniamines A and C were isolated together with 24 alpha-methylcholestanol, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, phenylacetic acid and 3-formylindole from the ethyl acetate extract of the marine sponge Oceanapia sagittaria (Sollas), collected from the Gulf of Thailand. Kuanoniamines A and C were evaluated for their effect on the growth of five human tumour and a non-tumour cell lines, as well as on the proliferation of human lymphocytes. Kuanoniamine A was found to be a potent growth inhibitor of all the tumour and a non-tumour cell lines while kuanoniamine C was less potent but showed high selectivity toward the estrogen dependent (ER+) breast cancer cell line. Kuanoniamine A has shown to be a more potent inhibitor of DNA synthesis than kuanoniamine C. Kuanoniamine A was also found to cause an extensive reduction of the MCF-7 cells in G2/M phase as well as an increase in the apoptotic cells.
ABSTRACT
The oligophenalenone dimer duclauxin and two new analogues, bacillisporins D and E, were isolated from the fungus TALAROMYCES BACILLISPORUS in addition to the previously reported bacillisporins A, B and C. Structures were established by spectroscopic studies. Duclauxin and bacillisporins A, B, C and E were evaluated for cytotoxicity against three human cancer cell lines. Bacillisporin A was strongly active against MCF-7 and NCI-H460 and moderately active against SF-268 while bacillisporins B, C and duclauxin were moderately active against all three cell lines.
Subject(s)
Cytotoxins/toxicity , Phenalenes/chemistry , Phenalenes/toxicity , Talaromyces/chemistry , Cell Line, Tumor , Chromones/chemistry , Chromones/isolation & purification , Chromones/toxicity , Cytotoxins/chemistry , Cytotoxins/isolation & purification , Dimerization , Humans , Nuclear Magnetic Resonance, Biomolecular , Phenalenes/isolation & purificationABSTRACT
The polyoxygenated clerodane, spiciflorin (1a), was isolated from Cleidion spiciflorum (Burm. f.) Merr. (Euphorbiaceae). Other constituents were the glucoside of anol (2), columbin, scopoletin, 3,3',4-O-trimethylellagic acid, acetylaleuritolic acid, common triterpenes and phenols.
Subject(s)
Diterpenes, Clerodane/chemistry , Euphorbiaceae/chemistry , Diterpenes, Clerodane/isolation & purification , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Extraction of roots and stems of Cleistanthus gracilis furnished common triterpenes, plant sterols and the unusual glucoside (+) gracicleistanthoside, the glucoside of 2-beta-hydroxy-8-azabicyclo-(5,2,0)-4beta,9beta-epoxynona-5,7-diene.
Subject(s)
Glucosides/isolation & purification , Malpighiaceae/chemistry , Glucosides/chemistry , Mass Spectrometry , Nuclear Magnetic Resonance, Biomolecular , Plant Roots/chemistry , Plant Stems/chemistryABSTRACT
5-Hydroxy-2-methoxyxanthone (1), 2-hydroxy-3-methoxyxanthone (2), trans-kielcorin (3), 4-hydroxy-3-methoxyphenyl ferulate (4) and 3beta-O-caffeoylbetulinic acid (5) were isolated from Hypericum hookerianum. Compounds 1-5 were tested against the growth of three human tumor cell lines, MCF-7, NCI-H460 and SF-268. Compounds 4 and 5 exhibited significant inhibitory activity effects against all three; GI50 values for 4 were 15.1 +/- 1.6, 18.7 +/- 2.3 and 15.9 +/- 2.7 and for 5 12.2 +/- 2.4, 19.6 +/- 2.3 and 24.3 +/- 2.5. Compound 3 was less active with GI50 values of 55.1 +/- 2.3, 49.7 +/- 3.0 and 40.5 +/- 1.5, while 1 and 2 exhibited only weak effects. Compounds 4 and 5 were moderately effective in influencing the mitogenic response to human lymphocytes to hemoagglutinin, with IC values of 26.1 +/- 3.6 and 40.8 +/- 4.9, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Hypericum , Phytotherapy , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Cinnamates/administration & dosage , Cinnamates/pharmacology , Cinnamates/therapeutic use , Esters/administration & dosage , Esters/pharmacology , Esters/therapeutic use , Humans , Inhibitory Concentration 50 , Lymphocytes/drug effects , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Xanthones/administration & dosage , Xanthones/pharmacology , Xanthones/therapeutic useABSTRACT
Aerial parts of Aconitum variegatum L. from the Pyrenees furnished four norditerpene alkaloids, 16 beta-hydroxycardiopetaline, 8-ethoxysachaconitine, 14-acetylgenicunine B, N-deethyl-N-19-didehydrosachaconitine, five diterpene alkaloids 15-veratroyldictizine, 15-veratroyl-17-acetyldictizine, 15-veratroyl-17-acetyl-19-oxodictizine, N-ethyl-1 alpha-hydroxy-17-veratroyldictizine, variegatine and the known alkaloids sachaconitine, 14-O-acetylsachaconitine, karakoline, talatizamine, 10-hydroxytalatizamine, 14-acetyltalatizamine, 14-acetyl-10-hydroxytalatizamine, N-methylarmepavine, pengshenin B, delsoline, dihydrodelsoline, delcosine and genicunin B. Structures of the alkaloids were established by MS, 1D- and 2D-NMR techniques.
Subject(s)
Aconitum/chemistry , Alkaloids/isolation & purification , Diterpenes/isolation & purification , Alkaloids/chemistry , Diterpenes/chemistry , Molecular StructureABSTRACT
Tissue cell cultures of Delphinium staphisagria L. produced three dianthramide glucosides N-(2'-beta-glucopyranosylsalicyl)-5-hydroxyanthranilic acid methyl ester, N-(2'-beta-glucopyranosyl-5'-methoxysalicyl)-5-hydroxyanthranilic acid methyl ester and N-(2'-beta-glucopyranosyl-5'-hydroxysalicyl)-5-hydroxy-6-methoxyanthranilic acid methyl ester, together with known methyl esters of N-salicylanthranilic acid and N-(2'-beta-glucopyranosyl-5'-hydroxysalicyl)-5-hydroxyanthranilic acid. Structures of the glucosides were established by MS, 1-D and 2-D NMR techniques.
Subject(s)
Delphinium/chemistry , Glucosides/isolation & purification , ortho-Aminobenzoates/isolation & purification , Cells, Cultured , Molecular StructureABSTRACT
Six known lupanes lupenone ( 1), 3- epi-lupeol ( 2), glochidone ( 4), glochidonol ( 5), glochidiol ( 6) and lup-20(29)-ene-1beta,3beta-diol ( 7) were isolated from the roots and stem wood of Glochidion eriocarpum and three, 5, 6 and lup-20(29)ene-3alpha,23-diol ( 3), were isolated from the roots and stem wood of Glochidion sphaerogynum. Compounds were identified by (1)H- and (13)C-NMR techniques. Triterpenes 2 - 7 were tested against the growth of three human tumor cell lines, MCF-7, NCI-H-460 and SF-268. Lupanes 3, 5, and 6 exhibited strong inhibitory effects against all three; thus GI (50) values for 3 were 12.7 +/- 3.7, 17.9 +/- 1.1 and 17.9 +/- 0.5, for 5 9.0 +/- 3.7, 4.9 +/- 0.2 and 9.8 +/- 0.5, and for 6 6.63 +/- 0.7, 7.5 +/- 0.5 and 9.7 +/- 0.3.3. Epilupeol was less active, with GI (50) values of 75.6 +/- 11.7, 86.1 +/- 12.4 and 80.9 +/- 2.6 while 7 was moderately active only against MCF-7 (GI (50) = 79.2 +/- 2.4). Additional studies indicated that triterpenes 5 and 6 exerted their antiproliferative activity through the involvement of apoptosis while triterpene 3 did not.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Phyllanthus , Phytotherapy , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor/drug effects , Humans , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Roots , Plant Stems , Triterpenes/administration & dosage , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/therapeutic useABSTRACT
A new friedolanostane, 7, and three triterpenes, 8, 9a, and 10, possessing the new 11(10-->8)-abeolanostane carbon skeleton were isolated from the bark of Garcinia speciosa. Structures were elucidated by spectroscopic and spectrometric studies and the structure of 8 by X-ray crystallographic analysis, thus forcing structure revision of a triterpene from the same source previously assumed to be a friedolanostane. These and several friedo- and lanostanes earlier isolated from the same source were evaluated for cytotoxicity against three human cell lines. Most were moderately active, with three friedolanostanes effective in inducing apoptosis in the MCF-7 cell line.
Subject(s)
Lanosterol/analogs & derivatives , Lanosterol/isolation & purification , Triterpenes/isolation & purification , Apoptosis/drug effects , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Lanosterol/chemistry , Lanosterol/pharmacology , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Bark/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Tumor Cells, CulturedABSTRACT
Aerial parts of a collection of Delphinium pentagynum Lam. from Niebla, Southern Spain, furnished one diterpene alkaloid, 2-dehydrodeacetylheterophylloidine, two norditerpene alkaloids, 14-demethyl-14-isobutyrylanhweidelphinine and 14-demethyl-14-acetylanhweidelphinine, the known alkaloids 14-deacetylnudicauline, methyllycaconitine, 14-deacetyl-14-isobutyrylnudicauline, 14-acetylbrowniine, browniine, delcosine, lycoctonine, 18-methoxygadesine, neoline, karakoline and the aporphine alkaloid magnoflorine. Structures of the alkaloids were established by MS, 1D and 2-D NMR techniques.
Subject(s)
Alkaloids/chemistry , Delphinium/chemistry , Alkaloids/isolation & purification , Chromatography, Agarose , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Plant Components, Aerial/chemistryABSTRACT
The CHCl(3) extract of the bark of Garcinia speciosa contained four 17,14-friedolanostanes and five lanostanes as well as friedelin and common plant constituents. The friedolanostanes were the previously known methyl ester of (24E)-3 alpha,23 alpha-dihydroxy-17,14-friedolanostan-8,14,24-trien-26-oic acid and the methyl esters of three hitherto unknown acids, 3 alpha-hydroxy-16 alpha,23 alpha-epoxy-17,14-friedolanostan-8,14,24-trien-26-oic acid, 3 alpha,23 alpha-dihydroxy-8 alpha,9 alpha-epoxy-17,14-friedolanostan-15-oxo-24-en-26-oic acid and 3 alpha,23 alpha-dihydroxy-17,14-friedolanostan-15-oxo-8(14),24-dien-26-oic acid. New lanostanes were 3 beta,9 alpha-dihydroxylanost-24-en-26-al and the methyl ester of 3 beta-hydroxy-23-oxo-9,16-lanostadien-26-oic acid. Structures were established by analysis of spectroscopic data. In the case of the lanostanes the previously unassigned C-25 stereochemistry was shown to be 25R by X-ray analysis of 3 beta-hydroxy-23-oxo-9,16-lanostadien-26-oic acid. In the case of the friedolanostanes the configuration at C-23 was established as 23R, identical with the absolute configuration at C-23 of mariesiic acids A and B.
Subject(s)
Garcinia/chemistry , Plant Bark/chemistry , Triterpenes/chemistry , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Stereoisomerism , Triterpenes/isolation & purification , X-Ray DiffractionABSTRACT
Aerial parts of Croton hieronymi furnished in addition to a large number of plant sterols and triterpenes the C-25 analog of trans-phytol, the squalene derivatives all-trans-2,6,15,19,23-pentamethyltetracosa-2,6,10,(28),14,22,28-hexaene-11-ol and all-trans-10-methylene-2,6,10,14,18,22-pentamethyltetracosa-1,6,10,14,18,22-hexaen-3-ol, the sesquiterpenes epicubenol and T-cadinol, the acetophenone derivative xanthoxylin and the peptide derivatives aurentiamide acetate and N-benzoylphenylalanyl-N-benzoylphenylalaninate.
Subject(s)
Croton/chemistry , Peptides/chemistry , Peptides/isolation & purification , Squalene/analogs & derivatives , Squalene/isolation & purification , Terpenes/isolation & purification , Plant Components, Aerial/chemistry , Sesterterpenes , Terpenes/chemistryABSTRACT
Wood of Horsfieldia irya contained 2-n-nonyl- and 2-(6-phenylhexyl)-5,7-dihydroxychromone, 2-n-nonyl-8-hydroxy- and 2-(6-phenylhexyl)-8-hydroxy-5,6,7,8-tetrahydrochromone as well as dihydrocubebin.
Subject(s)
Chromones/chemistry , Chromones/isolation & purification , Myristicaceae/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , WoodABSTRACT
Reexamination of the marine sponge Suberea aff. praetensa, (Row) from the Gulf of Thailand furnished in addition to bromotyrosine derivatives found previously 5-bromo- and 5-chlorocavernicolin, cavernicolins 1 and 2, two other brominated tyrosine metabolites, a known bisoxazolidone and a new unusual rearranged tyrosine metabolite subereatensin. Several of the metabolites exhibited significant inhibitory effects against five human cancer cell lines.