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N R Farnsworth

Publications and source records attributed to N R Farnsworth.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cytotoxic prenylated flavanones from Monotes engleri.

From the leaves of Monotes engleri, five prenylated flavanones were isolated as constituents that displayed cytotoxic activity against several human cancer cell lines. There of these substances are novel, namely, 6-(1,1-dimethylallyl)naringenin, 6-(1,1-dimethylallyl)eriodictyol and 3'-O-methyl-6-(1,1-dimethylallyl)-eriodictyol, with the other two active substances being the known flavanones, 6,8-diprenyleriodictyol and hiravanone. Additionally, two novel, but non-cytotoxic, biogenetically related flavanones were isolated, 6-[(2RS)-hydroxy-3-methyl-3-butenyl]-8-prenyleriodictyol and 5,4'-dihydroxy-4",4"-dimethyl-5"-methyl-5"H-dihydrofurano[2",3": 6,7]flavanone. The structures of the new compounds were determined by spectral analysis 1D- and 2D-NMR experiments.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Isolation and structure elucidation of ardisenone: a new, cytotoxic alkenylphenol from Ardisia iwahigensis.

A methanol extract of leaves and twigs from Ardisia iwahigensis demonstrated toxicity toward brine shrimp as well as LNCaP, ZR-75-1, and Lu1 human cancer cells in culture. A novel alkenylphenol, (Z)-1,16-bis(3-hydroxy-5-methoxyphenyl)-10-hexadecene-1,15-dione (ardisenone) (1), was isolated from the extract by bioassay-directed fractionation. This compound demonstrated moderate cytotoxicity against BC1, Lu1, Col2, KB, KB-V1, and LNCaP cell lines.

Animals↗
PubMed1997

Activity-guided isolation of constituents of Tephrosia purpurea with the potential to induce the phase II enzyme, quinone reductase.

An isoflavone, 7,4'-dihydroxy-3',5'-dimethoxyisoflavone (1), and a chalcone, (+)-tephropurpurin (2), both novel compounds, as well as six constituents of known structure, (+)-purpurin (3), pongamol (4), lanceolatin B (5), (-)-maackiain (6), (-)-3-hydroxy-4-methoxy-8,9-methylene-dioxypterocarpan (7), and (-)-medicarpin (8), were obtained as active compounds from Tephrosia purpurea, using a bioassay based on the induction of quinone reductase (QR) activity with cultured Hepa 1c1c7 mouse hepatoma cells. Additionally, three inactive compounds of known structure, 3'-methoxydaidzein, desmoxyphyllin B, and 3,9-dihydroxy-8-methoxycoumestan, were isolated and identified. The structure elucidation of compounds 1 and 2 was carried out by spectral data interpretation.

Animals↗
PubMed1996

Cell-cycle specific cytotoxicity mediated by rearranged ent-kaurene diterpenoids isolated from Parinari curatellifolia.

Two structurally novel cytotoxic ent-kaurene diterpenoids, 13-methoxy-15-oxozoapatlin and 13-hydroxy-15-oxozoapatlin, were isolated from the root bark of Parinari curatellifolia, together with the known compound, 15-oxozoapatlin, on the basis of bioactivity-guided chromatographic fractionation and found to demonstrate broad-spectrum cytotoxic activity against a panel of cultured human cancer cell lines. The structures of these compounds were determined by analysis of their spectroscopic data. The presence of an alpha, beta-unsaturated carbonyl group in 13-methoxy-15-oxozoapatlin suggested that the cytotoxic potential of this compound could be mediated through reaction with cellular nucleophiles by means of a Michael-type addition. The compound 13-methoxy-15-oxozoapatlin reacted with the nucleophiles L-cysteine and beta-mercaptoethanol. The adduct with beta-mercaptoethanol was isolated, structurally characterized and found to be approximately 5-fold less cytotoxic than 13-methoxy-15-oxozoapatlin itself. The compound 13-methoxy-15-oxozoapatlin did not interact with DNA nor guanosine, and it was not mutagenic for Salmonella typhimurium strain TM677. The effects of 13-methoxy-15-oxozoapatlin on the growth of human cancer cells were analyzed utilizing cultured ZR-75-1 breast cancer cells. Biosynthesis of DNA, RNA and protein was reduced in treated cells, and accumulation at the G2/M phase of the cell cycle was observed. The compound 13-methoxy-15-oxozoapatlin did not mediate antimitotic activity with dibutyryl cAMP-treated cultured astrocytoma cells, suggesting that the cell cycle effect is G2 specific. No antitumor activity was observed when athymic mice carrying KB cells were treated with 13-methoxy-15-oxozoapatlin. These data indicate that the cytotoxic activity of 13-methoxy-15-oxozoapatlin is mediated in part by covalent reaction with a cellular component (such as sulfhydryl-containing protein) by means of a Michael-type addition, and this results in the blockage of cell-cycle progression.

Africa↗
PubMed1996

Two new aromatic constitutents from the rootwood of Aeschynomene mimosifolia.

The rootwood of Aeschynomene mimosifolia Vatke (Leguminosae) has yielded a new neoflavonoid, mimosifoliol (1), and an unusual C16-styrylcycloheptenone derivative, mimosifolenone (2). The structures of these compounds were determined on the basis of spectral analysis. Compound 1 demonstrated weak activity in DNA-strand scission assay, while compound 2 was found to be inactive. Mimosifoliol (1) was inactive toward several human cell lines, while 2 was moderately active against the KB cell line.

Acrylates↗
PubMed1996

Nigranoic acid, a triterpenoid from Schisandra sphaerandra that inhibits HIV-1 reverse transcriptase.

An A ring-secocycloartene triterpenoid, nigranoic acid (3,4-secocycloarta-4(28),24-(Z)-diene-3,-26-dioic acid, (1) was isolated from the stems of Schisandra sphaerandra, a Chinese traditional medicinal plant. Its structure elucidation and unambiguous NMR spectral assignment were achieved by the combination of 1D- and 2D-NMR techniques with the aid of computer modeling. Nigranoic acid showed activity in several anti-HIV reverse transcriptase and polymerase assays.

China↗
PubMed1996

Costaricine, a new antiplasmodial bisbenzylisoquinoline alkaloid from Nectandra salicifolia trunk bark.

A MeOH extract of Nectandra salicifolia trunk bark, obtained during a diversity-based plant collection in a lower montane rainforest in Costa Rica, showed activity in an in vitro antiplasmodial assay measuring incorporation of [3H]-labeled hypoxanthie by Plasmodium falciparum. In addition to 15 known alkaloids isolated from samples of trunk bark, roots, and leaves/twigs of this species, a new bisbenzylisoquinoline alkaloid (+)-costaricine [(+)-12-O-methyllindoldhamine] (1) was isolated from bark (0.038% yield) and from roots (0.001%). (+)-Costaricine was active in the antiplasmodial assay, with IC50 values of 50 ng/mL vs. the chloroquine-sensitive D6 clone and 294 ng/mL vs. the chloroquine-resistant W2 clone of P. falciparum.

Alkaloids↗
PubMed1996

Antifungal and molluscicidal saponins from Serjania salzmanniana.

An investigation of Serjania salzmanniana for biologically active substances has led to the isolation of two novel saponins, salzmannianoside A (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] gypsogenin) [3] and salzmannianoside B (3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L- arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)] -alpha-L-arabinopyranosyl] hederagenin) (4). Two known saponins, pulsatilla saponin D (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] hederagenin) (1) and 3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-a lpha-L- arabinopyranosyl] oleanolic acid (2) were also isolated from this plant. The structures of 3 and 4 were elucidated by FABMS and 2D NMR techniques. All these four saponins were mollusicidal, causing 70-100% mortality at 10 ppm against Biomphalaria alexandrina, a vector of Schistosoma mansoni in the Nile Valley. The saponins also showed antifungal activity against Cryptococcus neoformans and Candida albicans at minimal inhibitory concentrations of 8 and 16 micrograms/mL, respectively.

Animals↗
PubMed1996

Lupane derivatives from Lophopetalum wallichii with farnesyl protein transferase inhibitory activity.

Chloroform-soluble extracts of the stems and of the mixed stems and stem bark of Lophopetalum wallichii were found to be inhibitory in a farnesyl protein transferase (FPTase) bioassay system. During the course of activity-guided fractionation, the known lupane-type triterpenes, ochraceolide A (1), ochraceolide B (2), betulin, and lupeol and the new lupane lactone, dihydro ochraceolide A (4), were isolated. The stereochemistry of the epoxide group of ochraceolide B (2) was determined by preparation of both epoxide isomers [2, and the new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The structure of 4 was established by reduction of 1 with sodium borohydride. Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay (IC50 values of 1.0 and 0.7 microgram/mL, respectively). Lupeol was found to be weakly active (IC50 65.0 micrograms/mL) in this test system, whereas no significant inhibition was detected for betulin or compounds 3 or 4. When evaluated against a panel of human cancer cells in culture, compounds 1 and 4 were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.

Alkyl and Aryl Transferases↗
PubMed1995

Cytotoxic biflavonoids from Selaginella willdenowii.

Bioactivity-guided fractionation of the leaves of Selaginella willdenowii afforded three known biflavones, 4',7"-di-O-methylamentoflavone, isocryptomerin and 7"-O-methylrobustaflavone, that were significantly cytotoxic against a panel of human cancer cell lines. Non-cytotoxic isolates were also obtained, namely, amentoflavone, bilobetin, robustaflavone and 2",3"-dihydroisocryptomerin, a new dihydrobiflavone. The structure for the new biflavonoid was unambiguously assigned by a combination of spectroscopic methods.

Antineoplastic Agents↗
PubMed1995

(-)-Roemerine, an aporphine alkaloid from Annona senegalensis that reverses the multidrug-resistance phenotype with cultured cells.

A known aporphine alkaloid, (-)-roemerine [1], isolated from the leaves of Annona senegalensis, was found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB-V1 cells. In the absence of vinblastine, no significant cytotoxicity was observed with KB-3 or KB-V1 cells (ED50 > 20 micrograms/ml), and several other human tumor cell lines were also relatively insensitive. As indicated by its ability to inhibit ATP-dependent [3H]vinblastine binding to multidrug-resistant KB-V1 cell membrane vesicles, (-)-roemerine appears to function by interacting with P-glycoprotein. In addition to alkaloid 1, three inactive compounds [the aporphine alkaloid(-)-isocorydine (reported in the levo-configuration for the first time), and the lignans (+/-)-8,8'-bisdihydrosiringenin [2] (a new natural product), and (+)-syringaresinol] were also isolated.

Africa↗
PubMed1995

Gummiferol, a cytotoxic polyacetylene from the leaves of Adenia gummifera.

A new polyacetylenic diepoxide compound, gummiferol [1] was isolated from the leaves of Adenia gummifera by KB cytotoxicity-guided fractionation. Compound 1 exhibited significant activity against the KB human cell line and a broad cytotoxic spectrum against other human cancer cell lines. The structure of 1 was established primarily on the basis of its spectral data.

Acetates↗
PubMed1995

Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis.

As a result of bioassay-guided fractionation, betulinic acid, a pentacyclic triterpene, was identified as a melanoma-specific cytotoxic agent. In follow-up studies conducted with athymic mice carrying human melanomas, tumour growth was completely inhibited without toxicity. As judged by a variety of cellular responses, antitumour activity was mediated by the induction of apoptosis. Betulinic acid is inexpensive and available in abundant supply from common natural sources, notably the bark of white birch trees. The compound is currently undergoing preclinical development for the treatment or prevention of malignant melanoma.

Animals↗
PubMed1995

Cytotoxic constituents of Bursera permollis.

Four cytotoxic lignans were isolated from the stem bark of Bursera permollis (Burseraceae), namely, deoxypodophyllotoxin (1), beta-peltatin methyl ether (2), picro-beta-peltatin methyl ether (3), and dehydro-beta-peltatin methyl ether (4). Also isolated was the inactive lignan, nemerosin (5). Compounds 1 and 2 were potently cytotoxic when evaluated against a panel of human cancer cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Plant antitumor agents. 31. The calycopterones, a new class of biflavonoids with novel cytotoxicity in a diverse panel of human tumor cell lines.

Three new biflavonoids to which we have accorded the trivial names calycopterone (1), isocalycopterone (2), and 4-demethylcalycopterone (3) and the known flavone 4',5-dihydroxy-3,3',6,7-tetramethoxyflavone (4) were isolated as cytotoxic constituents from the flowers of Calycopteris floribunda Lamk. (Combretaceae). Compounds 1-3 showed a wide range of activity against a panel of solid tumor cell lines. Among the biflavonoids, calycopterone (1) is the major constituent.

Animals↗
PubMed1994

Ethnopharmacology and drug development.

The value of ethanomedical information in drug development is based on several factors: accuracy in recording or observing the medical use of the ethnomedical preparation, whether or not the ethnomedical use can be corroborated under scientific conditions in the laboratory, the formal or informal experience of the practitioner who provides the information, the role of the placebo effect and perhaps many others. Published ethnomedical information has many strengths and weaknesses relative to the ability to establish a corresponding biological effect in the laboratory. Many of the publications contain insufficient detail for the laboratory scientist. The ability to correlate ethnomedical reports with corresponding scientific studies could lead to improved selection of plants for further study in the areas of arthritis, cancer, diabetes, epilepsy, hypertension, malaria, pain and fungal and viral infections. These analyses have been accomplished by computer analysis utilizing the NAPRALERT database. This combination of analysing ethnomedical information and published scientific studies on plant extracts (ethnopharmacology) may reduce the number of plants that need to be screened for drug discovery attempts, resulting in a corresponding greater success rate than by random selection and mass bioscreening.

Databases, Factual↗
PubMed1994

Cytotoxic clerodane diterpenes from Polyalthia barnesii.

Three cytotoxic clerodane diterpenes were purified from an ethyl acetate-soluble extract of the stem bark of Polyalthia barnesii, namely, 16 alpha-hydroxycleroda-3,13(14)Z-dien-15,16-olide, a known compound, and two novel compounds, 3 beta, 16 alpha-dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide and 4 beta, 16 alpha-dihydroxyclerod-13(14)Z-en-15,16-olide. These compounds were found to exhibit broad cytotoxicity against a panel of human cancer cell lines.

Antineoplastic Agents, Phytogenic↗