Showing papers in "Journal of Natural Products in 1989"
TL;DR: It is proposed that natural product/receptor interactions of sophistication comparable to enzyme/substrate interactions will be commonplace, and structures that are candidates to interact with known receptors can on occasion be suggested by inspection of the structures.
Abstract: We adopt the definition of a natural product as a substance that has no known role in the internal economy of the producing organism. The literature abounds with conflicting views for the existence of such natural products. We propose that all such structures serve the producing organisms by improving their survival fitness. We argue that this conclusion is necessitated by the fact that natural products are normally complex structures, whose biosynthesis is programmed by many kilobases of DNA. If it were otherwise, the pressures of Darwinian natural selection would have precluded the expenditure of so much metabolic energy in their construction and the development of such complexity. We further conclude that a natural product improves the producer's survival fitness by acting at specific receptors in competing organisms. Current studies of natural products interacting with receptors support this view, in terms of both the sophistication of the molecule/molecule recognition and the mechanistic details of physiological action. By the application of Occam's razor and general weaknesses of other hypotheses, these other hypotheses are rejected. It is a consequence of our proposal that natural product/receptor interactions of sophistication comparable to enzyme/substrate interactions will be commonplace. Additionally, structures that are candidates to interact with known receptors (e.g., double helical DNA) can on occasion be suggested by inspection of the structures. A range of evidence to support the general conclusions is presented.
342 citations
TL;DR: A potent tyrosine kinase inhibitor, lavendustin A, has been isolated from a butyl acetate extract of Streptomyces griseolavendus culture filtrate, and its structure is novel, having a tertiary amine in the center with substituted benzyl and phenyl groups.
Abstract: A potent tyrosine kinase inhibitor, lavendustin A [1], has been isolated from a butyl acetate extract of Streptomyces griseolavendus culture filtrate. It inhibits epidermal growth factor receptor-associated tyrosine kinase with an IC50 of 4.4 ng/ml, which is about 50 times more inhibitory than erbstatin. It does not inhibit protein kinase A or C. Its structure, determined by spectral data and total synthesis, is novel, having a tertiary amine in the center with substituted benzyl and phenyl groups. Lavendustin A competes with ATP and is noncompetitive with the peptide. Its structure-activity relationship is discussed.
245 citations
TL;DR: The isolation and structure elucidation of gedunin, the antimalarial agent of Azadirachta indica, are reported using one- and two-dimensional nmr spectroscopy, especially homonuclear and heteronuclear COSY, nOe difference, and COLOC experiments.
Abstract: The isolation and structure elucidation of gedunin [1], the antimalarial agent of Azadirachta indica, are reported. Its 1H- and 13C-nmr spectra were assigned by using one- and two-dimensional nmr spectroscopy, especially homonuclear and heteronuclear COSY, nOe difference, and COLOC experiments.
179 citations
153 citations
TL;DR: A reinvestigation of the bark of Uncaria tomentosa afforded, in addition to the major quinovic acid glycosides 1-3, three further glycoside 4-6, which were elucidated by spectral and chemical studies and a series of antiviral tests were performed.
Abstract: A reinvestigation of the bark of Uncaria tomentosa afforded, in addition to the major quinovic acid glycosides 1-3, three further glycosides 4-6. The structures were elucidated by spectral and chemical studies. Furthermore, a series of antiviral tests were performed on all these glycosides and on the related glycosides 7-9, previously isolated from Guettarda platypoda.
140 citations
TL;DR: Screening of crude extracts of the bark of Annona bullata showed cytotoxic and pesticidal activities and identified bullatacin as a diastereomer of asimicin, while the known compounds liriodenine and (-)-kaur-16-en-19-oic acid were lethal to brine shrimp but were not significantly cytot toxic.
Abstract: Screening of crude extracts of the bark of Annona bullata showed cytotoxic and pesticidal activities. By monitoring with brine-shrimp lethality, two novel, extremely potent acetogenins, bullatacin [1] and bullatacinone [2], were isolated. Spectral and chemical methods identified bullatacin as a diastereomer of asimicin. Bullatacinone represents bullatacin with the lactone cleaved and reformed at the 4-OH. Compounds 1 and 2 show selective cytotoxicities in human tumor cell lines, and certain susceptible cells give ED50 values as low as 10(-12)-10(-15) micrograms/ml. Bullatacin was pesticidal at concentrations as low as 1 ppm, but bullatacinone lacked pesticidal activities. The known compounds liriodenine and (-)-kaur-16-en-19-oic acid were also isolated and were lethal to brine shrimp but were not significantly cytotoxic.
120 citations
TL;DR: A series of 22 flavanoids and related compounds were tested for their ability to inhibit the activity of a protein-tyrosine kinase purified from bovine thymocytes (p40) andKinetic analyses indicated that the flavone apigenin [2] was a competitive inhibitor of p40 with respect to ATP.
Abstract: A series of 22 flavanoids and related compounds were tested for their ability to inhibit the activity of a protein-tyrosine kinase purified from bovine thymocytes (p40). Flavones or flavanols with hydroxyl groups at C-5 and C-7 or with three hydroxyl groups on the phenyl ring were potent inhibitors of p40. The replacement of hydroxyl groups with methoxyl groups led to a substantial loss of inhibitory activity. The presence of methoxyl or rhamnosyl substituents at C-3 also abolished inhibitory activity. Kinetic analyses indicated that the flavone apigenin [2] was a competitive inhibitor of p40 with respect to ATP. Flavanones and isoflavones were relatively inactive as protein-tyrosine kinase inhibitors. The isoflavone genistein [17], which has been reported as a potent inhibitor of both pp60(v=src) and the epidermal growth factor receptor, was not an inhibitor of p40.
106 citations
TL;DR: Bryophyllin B, a potent cytotoxic bufadienolide, has been isolated from Bryophyllum pinnatum and its structure confirmed by the use of 2D-nmr techniques and difference nOe method.
Abstract: Bryophyllin B [1], a potent cytotoxic bufadienolide, has been isolated from Bryophyllum pinnatum and its structure confirmed by the use of 2D-nmr techniques and difference nOe method. Transformation of bryotoxin C [2] to 1 with acid is also discussed.
105 citations
TL;DR: Hexane extracts of Hypericum drummondii showed significant activity against the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and the acid-fast bacterium Mycobacterium smegmatis in an agar well diffusion assay.
Abstract: Hexane extracts of Hypericum drummondii showed significant activity against the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and the acid-fast bacterium Mycobacterium smegmatis in an agar well diffusion assay. Employing bioassay-directed fractionation procedures, four new rottlerin-type compounds (drummondins A, B, C[1-3], and F [4]) were isolated and identified by spectral and physical characterization. The antimicrobial activity of these compounds was comparable to or greater than that demonstrated by streptomycin and generally correlated with cytotoxic activity determined with cultured P-388, KB, or human cancer cell lines (breast, colon, lung, melanoma). No cell-type selectivity was observed. In addition, two known compounds, albaspidins A-A [5] and P-P [6], were isolated and structured characterized. Neither demonstrated appreciable antimicrobial or cytotoxic activity.
98 citations
TL;DR: The inhibitory effect of 3 against DNA polymerases indicates that the selective antiviral action of 3 is determined by more than its action with HIV RT, and is comparable to their effects against the HIV RT at 30 microM and 10 microM, respectively.
Abstract: Four new tetragalloylquinic acids, 3,5-di-O-galloyl-4-O-digalloylquinic acid, 3,4-di-O-galloyl-5-O-digalloylquinic acid, 3-O-digalloyl-4,5-di-O-galloylquinic acid, and 1,3,4,5-tetra-O-galloylquinic acid, were isolated and characterized from a commercial tannic acid as a new class of human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitor. Compounds 2, 3, and 4 inhibit HIV RT activity 90, 89, and 84% at 100 microM and 73, 70, and 63% at 30 microM, respectively. Compounds 2-5 also inhibit the HIV growth in cells in the range of 61-70% with low cytotoxicity at 25 microM. The HIV cell growth inhibitory effects of these compounds at 25 microM and 6.25 microM (44-57%) are comparable to their effects against the HIV RT at 30 microM and 10 microM, respectively. The inhibitory effect of 3 against DNA polymerases indicates that the selective antiviral action of 3 is determined by more than its action with HIV RT.
91 citations
TL;DR: A new antibiotic has been obtained as the major metabolite produced in pure culture by Trichoderma koningii isolated from soil suppressive to the saprophytic growth of the take-all fungus, Gaeumannomyces graminis var.
Abstract: A new antibiotic has been obtained as the major metabolite produced in pure culture by Trichoderma koningii isolated from soil suppressive to the saprophytic growth of the take-all fungus, Gaeumannomyces graminis var. tritici. The structure of the compound, 4,8-dihydroxy-2-(1-hydroxyheptyl)-3,4,5,6,7,8-hexahydro-2H-1-benzopyran-5-one [2], has been deduced by spectroscopic methods that also allow the relative stereochemistry (2S*, 4R*, 8R*, 1'S*) to be assigned. The compound and broth culture containing the compound inhibited the growth of the take-all fungus in vitro. (…)
TL;DR: The taxonomy of the source organism for these styrylchromone natural products, 1 and 2, is revised to the marine cryptophyte Chrysophaeum taylori as a result of detailed microscopic and cultural efforts.
Abstract: Our previous chemical investigations of a yellow marine alga from Puerto Rico, tentatively identified as the tuft-forming cyanobacterium Hormothamnion enteromorphoides, led to the isolation of a structurally novel cytotoxic styrylchromone natural product, hormothamnione [2]. Continued chemical work with this organism has resulted in the isolation and spectroscopic structure elucidation of a closely related styrylchromone, 6-desmethoxyhormothamnione [1], which is also cytotoxic to cancer cells. The substitution pattern of proton, hydroxyl, and methoxyl groups on the chromone ring was established by long range 1H-13C heteronuclear correlation spectroscopy. The taxonomy of the source organism for these styrylchromone natural products, 1 and 2, is revised to the marine cryptophyte Chrysophaeum taylori as a result of detailed microscopic and cultural efforts.
TL;DR: For the first time, unambiguous 1H- and 13C-nmr assignments of compounds 1 and 2 are presented, as well as their in vitro cytotoxic activity against human tumor cell lines.
Abstract: The reisolation of nimbolide [1] from Azadirachta indica of Tanzanian origin and the isolation and structure elucidation of a new limonoid, 28-deoxonimbolide [2], from the same plant source are reported. For the first time, unambiguous 1H- and 13C-nmr assignments of compounds 1 and 2 are presented, as well as their in vitro cytotoxic activity against human tumor cell lines.
TL;DR: The investigation indicates that 9, 29, 32, 37, and 45 might be valuable anti-tumor promoters that significantly inhibit the EBV-EA activation at low doses.
Abstract: To search for possible antitumor promoters, we carried out a primary screening of fifty-one quinones (anthraquinones, naphthoquinones, azaanthraquinones, and azafluorenones) and related compounds, using their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of these quinones, notably 5-hydroxy-1,2-methylenedioxy-anthraquinone [9], shikonin [29], 2-acetylfuranonaphthoquinone [32], 5,8-dihydroxycleistopholine [37], and 5,8-dihydroxy-2-methyl-1-azaanthraquinone [45], were observed to significantly inhibit the EBV-EA activation at low doses. The position and number of hydroxyl groups on phenyl rings of these quinones affected the inhibitory activity on EBV-EA activation. The investigation indicates that 9, 29, 32, 37, and 45 might be valuable anti-tumor promoters.
TL;DR: The in vitro cytotoxicity (KB) appears to have no correlation with the inhibitory activity of the human DNA topoisomerase II, and the C-4 amino- and alkylamino-substituted 4'-demethyl-epipodophyllotoxins correlate reasonably well with their activity in causing protein-linked DNA breakage in KB cells.
Abstract: A series of analogues of etoposide, the C-4 amino- and alkylamino-substituted 4'-demethyl-epipodophyllotoxins, have been synthesized and studied for their activity to inhibit type II human DNA topoisomerase as well as their activity in causing cellular protein-linked DNA breakage. Substitution of the glycosidic moiety of 1 by a 2"-hydroxyethylamino or 2"-methoxyethylamino chain at the C-4 beta position resulted in potent inhibitors of the human DNA topoisomerase II. This inhibitory activity correlates reasonably well with their activity in causing protein-linked DNA breakage in KB cells. The in vitro cytotoxicity (KB) appears to have no correlation with the inhibitory activity of the human DNA topoisomerase II.
TL;DR: After it established that compounds 1-4 were neither acutely toxic with mice nor mutagenic with Salmonella typhimurium strain TM677, they were found by a human taste panel to exhibit sweetness potencies in the range 30-100 times greater than sucrose.
Abstract: In addition to abrusoside A [1], abrusosides B [2], C [3], and D [4], three further sweet glycosides based on the novel cycloartane-type aglycone, abrusogenin [5], were isolated from an n-BuOH-soluble extract of the leaves of Abrus precatorius. Using a combination of spectral methods, the structures of compounds 1-4 were assigned, respectively, as the 3-O-beta-D-glucopyranosyl, the 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-6-methylglucuronopyranosyl+ ++, the 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-glucopyranosyl, and the 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-glucuronopyranosyl derivatives of compound 5. After it established that compounds 1-4 were neither acutely toxic with mice nor mutagenic with Salmonella typhimurium strain TM677, they were found by a human taste panel to exhibit sweetness potencies in the range 30-100 times greater than sucrose.
TL;DR: The anti-inflammatory activities of the n-hexane extract of Sideritis javalambrensis and several purified fractions were investigated using the carrageenan mouse paw edema test and isolation of the active principles ent-16-hydroxy-13-epimanoyl oxide and esters of tyrosol with palmitic, stearic, behenic, and lignoceric acids was led to.
Abstract: The anti-inflammatory activities of the n-hexane extract of Sideritis javalambrensis and several purified fractions were investigated using the carrageenan mouse paw edema test. Progressive fractionation led to the isolation of the active principles ent-16-hydroxy-13-epimanoyl oxide [1] and esters of tyrosol with palmitic, stearic, behenic, and lignoceric acids.
TL;DR: 3,5-Dihydroxy-6,7,8-trimethoxyflavone, 3-O-methylquercetin, and helichrysetin were isolated from the flowers of the Rwandese medicinal plant, Helichrysum odoratissimum and shown to be an active principle as it displayed antimicrobial activity.
Abstract: 3,5-Dihydroxy-6,7,8-trimethoxyflavone, 3-O-methylquercetin, and helichrysetin were isolated from the flowers of the Rwandese medicinal plant, Helichrysum odoratissimum. Because of inconsistencies of the mp of the latter chalcone, a synthesis of helichrysetin was developed. 3-O-Methylquercetin was shown to be an active principle as it displayed antimicrobial activity.
TL;DR: The essential oil of Bupleurum fruticosum was investigated qualitatively and quantitatively together with the anti-inflammatory activity of the whole essential oil and its major components and antispasmodic activity was determined in rat uterus preparations using acetylcholine and oxytocin as agonists.
Abstract: The essential oil of Bupleurum fruticosum was investigated qualitatively and quantitatively together with the anti-inflammatory activity of the whole essential oil and its major components. In addition, antispasmodic activity was determined in rat uterus preparations using acetylcholine and oxytocin as agonists. The anti-inflammatory activity shown by the essential oil can be attributed in part to the two major components, alpha-pinene and beta-pinene, although the presence of thymol and carvacrol, minor components capable of potentiating the action of these hydrocarbons, was also confirmed.
TL;DR: Scale-up fermentation with Nocardia corallina and Penicillium chrysogenum has resulted in the production of two major microbial metabolites that have been characterized with the use of 2D-nmr techniques and have been identified as deoxyartemisinin and 3 alpha-hydroxydeoxyart Artemisinin.
Abstract: Microbial metabolism of the sesquiterpene lactone antimalarial drug artemisinin [1] was studied Screening studies have shown a number of microorganisms capable of metabolizing artemisinin [1] Scale-up fermentation with Nocardia corallina (ATCC 19070) and Penicillium chrysogenum (ATCC 9480) have resulted in the production of two major microbial metabolites that have been characterized with the use of 2D-nmr techniques These metabolites have been identified as deoxyartemisinin [2] and 3 alpha-hydroxydeoxyartemisinin [3]
TL;DR: The known styrylpyrone, goniotriol, has been isolated from Goniothalamus giganteus, and its structure and relative stereochemistry have been determined by X-ray crystallography as 6R-(7R,8R-Dihydro-7,8-dihydroxystyryl)-5S,6R-d Hudroxy-5-hydroxy-2-p yrone.
Abstract: The known styrylpyrone, goniotriol, has been isolated from Goniothalamus giganteus. Its bioactivities are reported, and its structure and relative stereochemistry have been determined by X-ray crystallography as 6R-(7R,8R-dihydro-7,8-dihydroxystyryl)-5S,6R-dihydro-5-hydroxy-2-p yrone.
TL;DR: Three novel perylenequinone pigments shiraiachromes A, B and C have been isolated from the Chinese bamboo fungus, Shiraia bambusicola and their structures have been determined on the basis of spectroscopic data and chemical correlations.
Abstract: Three novel perylenequinone pigments shiraiachromes A, B and C have been isolated from the Chinese bamboo fungus, Shiraia bambusicola. Their structures (cyclohepta [ghi] perylene dione-5,12) have been determined on the basis of spectroscopic data and chemical correlations
TL;DR: Arjunolic acid, an oleanene-type triterpene isolated from the rhizome of Cochlospermum tinctorium, its triacetate derivative, and their methyl esters were tested and their inhibitory effects on skin tumor promotors were found to be greater than those of previously studied natural products.
Abstract: Arjunolic acid, an oleanene-type triterpene isolated from the rhizome of Cochlospermum tinctorium, its triacetate derivative, and their methyl esters were tested using the short-term in vitro assay on EBV-EA activation in Raji cells induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA). Their inhibitory effects on skin tumor promoters were found to be greater than those of previously studied natural products.
TL;DR: The fungus Alternaria alternata was found to be a host-selective pathogen of spotted knapweed; Centaurea maculosa, a major weed pest in rangelands of the northwestern United States and southwestern Canada, and two of the perylenequinones, alterlosins I and II, are new compounds.
Abstract: The fungus Alternaria alternata was found to be a host-selective pathogen of spotted knapweed; Centaurea maculosa, a major weed pest in rangelands of the northwestern United States and southwestern Canada. Examination of the extracts of fungal cultures revealed three classes of phytotoxins-diketopiperazines, tetramic acids, and perylenequinones. The isolation, identification, and phototoxic activity of the tetramic acid and perylenequinones are described; two of the perylenequinones, alterlosins I and II, are new compounds. (…)
TL;DR: The structure of a new glycoside, eryloside A, isolated from the Red Sea sponge Erylus lendenfeldi, has been determined by 1D and 2D nmr techniques.
Abstract: The structure of a new glycoside, eryloside A [1], isolated from the Red Sea sponge Erylus lendenfeldi, has been determined by 1D and 2D nmr techniques.
TL;DR: In this paper, a saturated pyrrolizidine-type alkaloid was isolated from tall fescue (Festuca arundinacea) seed infected with the endophytic fungus Acremonium coenophialum.
Abstract: Loline, a saturated pyrrolizidine-type alkaloid, was isolated from tall fescue (Festuca arundinacea) seed infected with the endophytic fungus Acremonium coenophialum. Procedures are described for the efficient conversion of loline to derivatives also known to occur naturally. The loline akaloids are of interest as they are suspected contributors to several disease syndromes in cattle that consume endophypte-infected tall fescue
TL;DR: Matesaponin 1, a new saponin obtained from the leaves of Ilex paraguariensis, has been characterised by 1 H nmr, 13 C nmR, eims, fabms, and chemical reactions.
Abstract: Matesaponin 1, a new saponin obtained from the leaves of Ilex paraguariensis, has been characterised by 1 H nmr, 13 C nmr, eims, fabms, and chemical reactions