Showing papers by "John M. Pezzuto published in 1998"
TL;DR: It is found that resveratrol also directly inhibited the activity of COX-2, a phenolic antioxidant found in grapes and other food products, which is likely to be important for understanding the anti-cancer and anti-inflammatory properties of resver atrol.
773 citations
Journal Article•
TL;DR: Of these substances, the hydroxystilbenes piceatannol and transresveratrol have thus far been shown to inhibit carcinogen-induced preneoplastic lesion formation in the mouse mammary gland organ culture model.
Abstract: Since reactive oxygen radicals play an important role in carcinogenesis and other human disease states, antioxidants present in consumable fruits, vegetables, and beverages have received considerable attention as cancer chemopreventive agents Thus, in order to identify antioxidants in plant extracts, test materials were assessed for potential to scavenge stable 1,2-diphenyl-2-picrylhydrazyl (DPPH) free radicals, reduce TPA-induced free radical formation in cultured HL-60 human leukemia cells, and inhibit responses observed with a xanthine/xanthine oxidase assay system Approximately 700 plant extracts were evaluated, and 28 were found to be active in the DPPH free radical scavenging assay Based on secondary analyses performed to assess inhibition of 7,12-dimethylbenz(a)anthracene-induced preneoplastic lesion formation with a mouse mammary organ culture model, Chorizanthe diffusa Benth (Polygonaceae), Mezoneuron cucullatum Roxb (Leguminosae), Cerbera manghas L (Apocynaceae) and Daphniphyllum calycinum Benth (Daphniphyllaceae) were selected and subjected to bioassay-guided fractionation 5,7,3',5'-Tetrahydroxy-8,4'-dimethoxyflavonol, 5,8,4'-trihydroxy-7,3'-dimethoxyflavonol, 5,3',4'-trihydroxy-7-methoxyflavonol, and 6,3',4'-trihydroxy-7-methoxyflavonol were identified as active principles from C diffusa Piceatannol, trans-resveratrol, apigenin and scirpusin A were found as the active principles of M cucullatum, olivil, (-)-carinol, and (+)-cycloolivil were active principles from C manghas, and 5,6,7,4'-tetrahydroxyflavone 3-O-rutinoside and kaempferol 3-O-neohesperidoside were active principles from D calycinum Of these substances, the hydroxystilbenes piceatannol and transresveratrol have thus far been shown to inhibit carcinogen-induced preneoplastic lesion formation in the mouse mammary gland organ culture model
491 citations
TL;DR: The data suggest that resveratrol inhibits tumorigenesis in mouse skin through interference with pathways of reactive oxidants and possibly by modulating the expression of c-fos and TGF-beta1.
152 citations
TL;DR: This preliminary investigation demonstrates that simple modifications of the parent structure of betulinic acid can produce potentially important derivatives, which may be developed as antitumor drugs.
146 citations
TL;DR: Novel 1H-cyclopenta[b]benzofuran lignans are potent cytostatic inhibitors of protein biosynthesis and are capable of delaying tumor growth in an in vivo model and their full clinical or basic utility requires further investigation.
129 citations
TL;DR: A novel flavonoid diglycoside and a previously known compound were isolated from an ethyl acetate extract of Daphniphyllum calycinum leaves that showed significant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay.
Abstract: A novel flavonoid diglycoside, 5,6,7,4'-tetrahydroxyflavonol 3-O-rutinoside (1), and a previously known compound, kaempferol 3-O-neohesperidoside (2), were isolated from an ethyl acetate extract of Daphniphyllum calycinum leaves that showed significant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay. The structure of 1 was elucidated by a combination of spectroscopic methods, and compounds 1 and 2 were found to be moderately active as antioxidants in the DPPH assay.
117 citations
TL;DR: When evaluated for potential to inhibit TPA-induced JB6 cell transformation, several of the metabolites mediated inhibitory responses greater than sarcophytol A or sarcophine, most notably 7alpha-hydroxy-Delta(8(19))-deepoxysarcophine (6), which was comparable to 13-cis-retinoic acid.
Abstract: Sarcophytol A (1) and B (2) (see Chart 1) are cembrane-type diterpenes known to inhibit tumor promotion. Indicative of this inhibitory response, we currently report sarcophytol A (1) mediates dose-dependent diminution of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced transformation of JB6 cells. Moreover, a structurally related furanocembrane diterpene, sarcophine (3), isolated in good yield from the Red Sea soft coral Sarcophyton glaucum, was also found to serve as an effective inhibitor of JB6 cell transformation. This compound was subjected to preparative-scale fermentation with Absidia glauca ATCC 22752, Rhizopus arrhizus ATCC 11145, and Rhizopus stolonifer ATCC 24795, resulting in the production of 10 new metabolites (5−14) along with the known compound 7β,8α-dihydroxydeepoxysarcophine (4). Structures were elucidated primarily on the basis of 2D-NMR spectroscopy, with X-ray crystallography being used to establish the relative stereochemistry of metabolite 5. When evaluated for potential to inhibi...
83 citations
TL;DR: In a comprehensive series of studies performed with various PKC isozymes derived from a variety of mammalian species, neither chelerythrine nor angoline inhibited activity with high potency, and mechanisms independent of PKC inhibition should be considered as responsible for these effects.
67 citations
Patent•
09 Jan 1998
TL;DR: In this paper, a method of cancer chemoprevention using resveratrol as a cancer chemoreventive agent in mammals, including humans, is described. But the method is not described.
Abstract: A composition and method of cancer chemoprevention is disclosed. The composition and method utilize resveratrol as a cancer chemopreventative agent in mammals, including humans.
59 citations
TL;DR: An ethyl acetate extract derived from the seeds of the medicinal and food plant Casimiroa edulis inhibited mutagenicity induced by 7,12-dimethylbenz[a]anthracene (DMBA) with Salmonella typhimurium strain TM677 as mentioned in this paper.
Abstract: An ethyl acetate extract derived from the seeds of the medicinal and food plant Casimiroa edulis inhibited mutagenicity induced by 7,12-dimethylbenz[a]anthracene (DMBA) with Salmonella typhimurium strain TM677. It also showed complete inhibition of DMBA-induced preneoplastic lesions with an in vitro mouse mammary gland organ culture system at a concentration of 10 μg/mL. Bioassay-guided phytochemical investigation of this extract using antimutagenicity as a monitor led to the isolation of four furocoumarins, constituted by the known compounds phellopterin (1) and isopimpinellin (2) and the novel compounds (R,S)-5-methoxy-8-[(6,7-dihydroxy-3,7-dimethyl-2-octenyl)oxy]psoralen (3) and (R,S)-8-[(6,7-dihydroxy-3,7-dimethyl-2-octenyl)oxy]psoralen (4). Four known alkaloids, casimiroin (5), 4-methoxy-1-methyl-2(1H)-quinolinone (6), 5-hydroxy-1-methyl-2-phenyl-4-quinolone (7), and γ-fagarine (8), and two known flavonoids, zapotin (9) and 5,6,2‘-trimethoxyflavone (10), were also isolated. Of these isolates, compoun...
55 citations
TL;DR: Four novel steroidal alkaloids were isolated from Pachysandra procumbens using a bioassay-guided fractionation based on inhibition of 3H-tamoxifen binding at the antiestrogen binding site (AEBS), and compounds 1-7 demonstrated significant activity as AEBS-inhibitory agents.
Abstract: Four novel steroidal alkaloids, (+)-(20S)-20-(dimethylamino)-3-(3'alpha-isopropyl)-lactam-5alpha-+ ++preg n-2-en-4-one (1), (+)-(20S)-20-(dimethylamino)-16alpha-hydroxy-3-(3'alpha-isopropyl) -la ctam-5alpha-pregn-2-en-4-one (2), (+)-(20S)-3-(benzoylamino)-20-(dimethylamino)-5alpha-pregn-2-en-++ +4beta -yl acetate (3), and (+)-(20S)-2alpha-hydroxy-20-(dimethylamino)-3beta-phthalimido-5 alpha- pregnan-4beta-yl acetate (4), as well as five known compounds, (-)-pachyaximine A (5), (+)-spiropachysine (6), (+)-axillaridine A (7), (+)-epipachysamine D (8), and (+)-pachysamine B (9), were isolated from Pachysandra procumbens, using a bioassay-guided fractionation based on inhibition of 3H-tamoxifen binding at the antiestrogen binding site (AEBS). Compounds 1-7 and 9 demonstrated significant activity as AEBS-inhibitory agents, and compounds 3, 5 and 9 were found to potentiate significantly the antiestrogenic effect mediated by tamoxifen in cultured Ishikawa cells. The structure elucidation of compounds 1-4 was carried out by spectral data interpretation.
TL;DR: In this paper, the structures were assigned on the basis of spectral and chemical studies and the compounds were evaluated for their cytotoxic activity for Euclea divinorum, including lupeol, lupene, betulin, 7-methyljuglone, isodiospyrin, shinalone, catechin and 3β-(5-hydroxyferuloyl)lup-20(30)-ene.
TL;DR: Two new cytotoxic compounds, 2-[10(Z)-heptadecenyl]-1,4-hydroquinone and (4R,6R)-dihydroxy-4-[10 (Z)- heptadeCenyl]2-cyclohexenone, have been isolated from a MeOH extract of seeds of Tapirira guianensis.
Abstract: Two new cytotoxic compounds, 2-[10(Z)-heptadecenyl]-1,4-hydroquinone (1) and (4R,6R)-dihydroxy-4-[10(Z)-heptadecenyl]-2-cyclohexenone (2) have been isolated from a MeOH extract of seeds of Tapirira guianensis. The structures were established through spectral analysis of the isolates and their derivatives.
Patent•
14 May 1998TL;DR: In this paper, a composition and method of preventing or inhibiting tumor growth, and of treating malignant cancers without toxic side effects are disclosed, and the active compound of the composition is either a Betulinic acid or a Betulusic acid derivative.
Abstract: A composition and method of preventing or inhibiting tumor growth, and of treating malignant cancers without toxic side effects are disclosed. Betulinic acid or a betulinic acid derivative is the active compound of the composition.
TL;DR: 1,2-Dimethoxy-5-hydroxyxanthone was isolated from the twigs of Mammea siamensis, in addition to six known xanthones, and structures for these compounds were deduced from their spectral data.
TL;DR: Activity-directed fractionation of a stem extract of Azadirachta excelsa using KB (human oral epidermoid carcinoma) cells led to the isolation of four meliacin-type limonoids, which were purified along with the known compounds, nimbolide and 28-deoxonimbolides and two novel compounds.
TL;DR: The chemopreventive potential of resveratrol was examined by investigating its effect on cyclooxygenase (COX) metabolites monitored by HPLC analysis and this compound significantly inhibited malignant transformation induced by chemical carcinogens in the mouse C3H10T1/2 cell culture system.
Abstract: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit 7,12‐dimethylbenz[a]anthracene-induced preneoplastic lesions in mouse mammary organ culture and 12O-tetradecanoylphorbol-13-acetate-promoted mouse skin tumors. It has been postulated that resveratrol may inhibit tumorigenesis in mouse skin through interference with reactive oxidant pathways, and possibly by modulating the expression of c-fos and TGF-s1. The chemopreventive potential of resveratrol was further examined by investigating its effect on cyclooxygenase (COX) metabolites monitored by HPLC analysis. Resveratrol was found to inhibit the generation of arachidonic acid metabolites catalyzed by both COX-1 and COX-2. In addition, this compound significantly inhibited malignant transformation induced by chemical carcinogens in the mouse C3H10T1/2 cell culture system. These data serve to corroborate the cancer chemopreventive potential of resveratrol.
TL;DR: This article showed that simple modifications of the parent structure of betulinic acid can produce potentially important derivatives, which may be developed as antitumor drugs and evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines.
Abstract: Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of betulinic acid can produce potentially important derivatives, which may be developed as antitumor drugs.
Patent•
06 Apr 1998TL;DR: In this article, a composition and method of preventing or inhibiting tumor growth, and of treating malignant melanoma, without toxic side effects are disclosed Betulinic acid or a betulinic-acid derivative is the active compound of the composition, which is topically applied to the situs of tumor.
Abstract: A composition and method of preventing or inhibiting tumor growth, and of treating malignant melanoma, without toxic side effects are disclosed Betulinic acid or a betulinic acid derivative is the active compound of the composition, which is topically applied to the situs of tumor
TL;DR: Activity-guided fractionation of a stem extract of Mezzettia leptopoda using human oral epidermoid carcinoma (KB) cells led to the isolation of seven highly acylated oligorhamnosides, four of which are novel and found to be weakly cytotoxic toward KB and/or human colon and lung cancer cell lines.
Abstract: Activity-guided fractionation of a stem extract of Mezzettia leptopoda using human oral epidermoid carcinoma (KB) cells led to the isolation of seven highly acylated oligorhamnosides. Four of these...
TL;DR: From the leaves of Isodon megathyrsus, a novel ent-kaurene diterpene, megathyrin B, was isolated and its structure determined as 1 alpha,7 beta,11 beta,15 beta-tetrahydroxy-ent-7 alpha,20-epoxy-kaur-16-ene by 1D- and 2D-NMR spectral analysis.
Abstract: From the leaves of Isodon megothyrsus, a novel entkaurene diterpene, megathyrin B, was isolated and its structure determined as 1 alpha,7 beta,11 beta,15 beta-tetrahydroxy-ent-7 alpha,20-epoxykaur-16-ene by 1D- and 2D-NMR spectral analysis. Additionally, its stereochemistry was unambiguously assigned by X-ray crystallography. This compound was cytotoxic to the KB and KB-V cell lines.
Patent•
26 Mar 1998
TL;DR: Improved methods of manufacturing betulinic acid from betulin are disclosed in this article, which provide the β-isomer of betulinIC acid in high purity and high yield, respectively.
Abstract: Improved methods of manufacturing betulinic acid from betulin are disclosed. The methods provide the β-isomer of betulinic acid in high purity and high yield.
Patent•
26 Mar 1998
TL;DR: In this paper, a procedure for the production of β-isomere de l'acide betulinique sous une forme tres pure is described, a procedure that can permettent a production a haut rendement du β-ISomere of l'ACIDE betuline sous a forme Tres pure.
Abstract: Cette invention se rapporte a des procedes perfectionnes de production d'acide betulinique a partir de betuline. Ces procedes permettent une production a haut rendement du β-isomere de l'acide betulinique sous une forme tres pure.
Patent•
14 May 1998
TL;DR: In this paper, a composition actif de la composition est l'acide betulinique or un derive d'ACide betulainique, and le compose actif of the composition is l'actif actif d'acides betuliniques.
Abstract: L'invention concerne une composition et un procede permettant d'eviter ou d'inhiber la croissance de tumeurs, et de traiter des tumeurs malignes sans effets secondaires toxiques. Le compose actif de la composition est l'acide betulinique ou un derive d'acide betulinique.