Showing papers in "Journal of Natural Products in 1993"
TL;DR: The stimulation of both antigen specific and nonspecific immune response was, however, of lower order with andrographolide than with the EtOH extract, suggesting thereby that substance(s) other than andrograpolide present in the extract may also be contributing towards immunostimulation.
Abstract: EtOH extract and purified diterpene andrographolides of Andrographis paniculata (Acanthaceae) induced significant stimulation of antibody and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) in mice. The plant preparations also stimulated nonspecific immune response of the animals measured in terms of macrophage migration index (MMI) phagocytosis of 14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and nonspecific immune response was, however, of lower order with andrographolide than with the EtOH extract, suggesting thereby that substance(s) other than andrographolide present in the extract may also be contributing towards immunostimulation.
411 citations
TL;DR: A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay.
Abstract: A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 microM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3], arteether [4], sodium artesunate [5], artelinic acid [6], and sodium artelinate [7]), exhibited a somewhat more potent cytotoxicity. Their IC50 values ranged from 12.2 to 19.9 microM. The presence of an exocyclic methylene fused to the lactone ring, as for artemisitene [9], led to higher cytotoxicity than 1. From the two epimeric 11-hydroxyartemisinin derivatives, the R form 12 showed a considerably higher cytotoxicity than the S form 13. Opening of the lactone ring of 1 dramatically reduced the cytotoxicity. The ether dimer 8 of 2 was the most potent cytotoxic agent, its IC50 being 1.4 microM. The variations in cytotoxicity between the structurally related compounds mostly correlated well with the theoretical capacity of radical formation and stabilization. In some cases lipophilicity or the presence of an electrophilic moiety seemed to have a determinant influence on cytotoxicity. The artemisinin-related endoperoxides showed cytotoxicity to EAT cells at higher concentrations than those needed for in vitro antimalarial activity, as reported in the literature.
274 citations
TL;DR: In responding to the drug supply crisis which emerged with the demonstration of the clinical efficacy of taxol, the NCI has developed plans to avert similar supply crisis in the future by initiating exploratory research projects for large-scale production of promising agents at the earliest possible point following the demonstrated antitumor activity.
Abstract: Over the past 30 years, the National Cancer Institute has been involved in the preclinical and/or clinical evaluation of the majority of those agents approved for the treatment of cancer. Many of the new agents under consideration in the NCI program are either natural products or derivatives of natural product leads, and of critical importance to their development is the issue of drug supply. In responding to the drug supply crisis which emerged with the demonstration of the clinical efficacy of taxol, the NCI has identified several important lessons for those interested in natural product drug discovery and development. As a result, the NCI has developed plans to avert similar supply crisis in the future by initiating exploratory research projects for large-scale production of promising agents at the earliest possible point following the demonstration of confirmed antitumor activity. These plans, together with a review of the development of taxol, are presented in this paper.
271 citations
TL;DR: Comparison of the IC50 values of resveratrol for protein-tyrosine kinase inhibitory activity with those of piceid and res veratrol-O4'-beta-glucoside shows the requirement of free hydroxyl groups on both phenyl rings for the Protein kinase C inhibitory analysis suggests the requirements of two free hydroxy groups on one phenyl ring only.
Abstract: Bioassay-directed fractionation of a medicinal plant, Polygonum cuspidatum (Polygonaceae), has led to the discovery of a hydroxystilbene, resveratrol [1], as an inhibitor of a protein-tyrosine kinase (p56lck) partially purified from bovine thymus. Both trans and cis isomers of resveratrol possess comparable protein-tyrosine kinase inhibitory activity. Comparison of the IC50 values of resveratrol for protein-tyrosine kinase inhibitory activity with those of piceid (resveratrol-O3-beta-glucoside) [2] and resveratrol-O4'-beta-glucoside [3] shows the requirement of free hydroxyl groups on both phenyl rings for the protein-tyrosine kinase inhibition. Protein kinase C inhibitory analysis suggests the requirements of two free hydroxyl groups on one phenyl ring only.
245 citations
TL;DR: (+)-2-N-Methyltelobine, a new alkaloid, together with twelve known bisbenzylisoquinolines, was isolated from the tubers of Stephania erecta and did not appear to be promising clinical candidates at the present time.
Abstract: (+)-2-N-Methyltelobine [1], a new alkaloid, together with twelve known bisbenzylisoquinolines, was isolated from the tubers of Stephania erecta. The structure determination and the complete 1H- and unambiguous 13C-nmr assignments of 1 were obtained through extensive use of several 1D and 2D nmr techniques. All alkaloids inhibited the growth of cultured Plasmodium falciparum strains D-6 and W-2 and displayed nonselective cytotoxicity with a battery of cultured mammalian cells. These data were used for the calculation of selectivity indices. Relative to known antimalarial agents, these bisbenzylisoquinoline alkaloids do not appear to be promising clinical candidates at the present time.
241 citations
TL;DR: A new alkaloid (-)-amabiline was isolated from the bulbs of Crinum amabile (Amaryllidaceae), and alkaloids 2, 4, and 5 were found to be the principal cytotoxic and antimalarial constituents.
Abstract: From the bulbs of Crinum amabile (Amaryllidaceae), a new alkaloid (-)-amabiline [1], together with the known alkaloids (-)-lycorine [2], (-)-buphanisine [3], (-)-augustine [4], and (+)-crinamine [5], were isolated. The structural characterization of 1 and the revised 1H- and 13C-nmr assignments of 2 are discussed. Alkaloids 2, 4, and 5 were found to be the principal cytotoxic and antimalarial constituents.
182 citations
TL;DR: Serum lipid levels in rats with hyperlipidemia induced by diet as well as by Triton were determined after oral administration of EtOAc extract of Pterocarpus marsupium heartwood and its flavonoid constituents, marsupsin, pterosupin, and liquiritigenin, with pterOSupin being additionally effective in lowering serum triglyceride.
Abstract: Serum lipid levels in rats with hyperlipidemia induced by diet as well as by Triton were determined after oral administration of EtOAc extract of Pterocarpus marsupium heartwood and its flavonoid constituents, marsupsin [1], pterosupin [2], and liquiritigenin [3]. Administration of EtOAc extract for 14 consecutive days produced a significant reduction of serum triglyceride, total cholesterol, and LDL- and VLDL-cholesterol levels without any significant effect on the level of HDL-cholesterol. Liquiritigenin and pterosupin were able to effect a significant fall in serum cholesterol, LDL-cholesterol, and atherogenic index, pterosupin being additionally effective in lowering serum triglyceride.
140 citations
TL;DR: Anti-HIV-active polysaccharides and polyphenols were isolated from the brown seaweed Fucus vesiculosus by hot H2O extraction and tested for inhibition of both HIV-induced syncytium formation and HIV reverse transcriptase enzyme activity.
Abstract: Anti-HIV-active polysaccharides and polyphenols were isolated from the brown seaweed Fucus vesiculosus by hot H2O extraction of both the intact and the homogenized algae. This was followed by XAD2 chromatography and by sequential precipitation of the non-adsorbed compounds with glacial HOAc and thereafter with EtOH. The precipitate was solubilized, dialyzed against distilled H2O, and chromatographed on SP-Sephadex C25 and on QAE-Sephadex A25. This was followed by gel filtration on Sephadex G50 and Sephadex G100 and finally by hplc on a Shodex Ionpak S-804 column. For comparison, the commercial product fucoidan, a sulfated algal polysaccharide, was also further purified by the chromatographic techniques mentioned above. The isolated freeze-dried fractions obtained by these procedures were tested for inhibition of both HIV-induced syncytium formation and HIV reverse transcriptase enzyme activity. Some of these fractions inhibited both of these activities at concentrations that were not cytotoxic.
136 citations
TL;DR: A detailed examination of the metabolites produced in liquid cultures by a strain of Trichoderma harzianum, isolated from wheat roots, has resulted in the identification of five metabolites that show antibiotic activity towards the take-all fungus, Gaeumannomyces graminis var.
Abstract: A detailed examination of the metabolites produced in liquid cultures by a strain of Trichoderma harzianum, isolated from wheat roots, has resulted in the identification of a further five metabolites. Two of these, cyclonerodiol [5] and the octaketide keto diol 6, have previously been isolated from a strain of Trichoderma koningii. The structures of the three new octaketide-derived compounds 7, 8, and 10 have been deduced from spectroscopic and chemical studies. All newly isolated compounds show antibiotic activity towards the take-all fungus, Gaeumannomyces graminis var. tritici.
133 citations
TL;DR: Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3'O-dimethylcedrusin or 4-O-methyldihydrodehydrodiconiferyl alcohol as the biologically active principle.
Abstract: Dragon's blood is a red viscous latex extracted from the cortex of various Croton spp. (Euphorbiaceae), most commonly Croton lechleri, Croton draconoides (or Croton palanostigma), and Croton erythrochilus. It is used in South American popular medicine for several purposes, including wound healing. Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3',4-O-dimethylcedrusin or 4-O-methyldihydrodehydrodiconiferyl alcohol [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-methoxybenzo furan-5- propan-1-ol] [1] as the biologically active principle. A related compound, 4-O-methylcedrusin [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzo furan-5- propan-1-ol] [2], and the alkaloid taspine [3], also isolated from dragon's blood, were not active in the same assay. A cell proliferation assay, measuring the incorporation of tritiated thymidine in endothelial cells, showed that compound 1 did not stimulate cell proliferation, but rather inhibited thymidine incorporation, while protecting cells against degradation in a starvation medium.
128 citations
TL;DR: Although there were striking differences in overall potency, some of the compounds shared a highly characteristic differential cytotoxicity profile against the 60 diverse human tumor cell lines comprising the NCI panel, as a group, the melanoma subpanel lines were most sensitive.
Abstract: The bulbs of Hymenocallis littoralis, collected in Hawaii and horticulturally grown in Arizona, and bulbs of Hymenocallis caribaea and Hymenocallis latifolia, collected in Singapore, were found to contain a cytotoxic, isocarbostyril-type biosynthetic product, 7-deoxy-trans-dihydronarciclasine [2]. This new compound inhibited the cytopathicity and/or replication of various viruses. Companion cytotoxic constituents of H. littoralis and Hymenocallis sp. were found to be pancratistatin [1], narciclasine [5], and 7-deoxynarciclasine [4]. These four compounds, along with four other closely related compounds, were comparatively evaluated in the National Cancer Institute's in vitro cytotoxicity panel. Although there were striking differences in overall potency, some of the compounds shared a highly characteristic differential cytotoxicity profile against the 60 diverse human tumor cell lines comprising the NCI panel. As a group, the melanoma subpanel lines were most sensitive; certain individual lines within other subpanels (eg., NSC lung, colon, brain, renal) were as much as a thousand-fold or more sensitive than the less sensitive lines.
TL;DR: A hot-H2O extract of rhizomes of Anemarrhena asphodeloides, the Japanese sino-medicine "chimo," lowered the blood glucose level in alloxan-diabetic mice, suggesting that the hypoglycemic mechanism may be due to inhibition of hepatic gluconeogenesis and/or glycogenolysis.
Abstract: A hot-H2O extract of rhizomes of Anemarrhena asphodeloides, the Japanese sino-medicine "chimo," lowered the blood glucose level in alloxan-diabetic mice. Hypoglycemic activity-guided fractionation isolated a new glycoside, pseudoprototimosaponin AIII [1], which was compared with chemically known prototimosaponin AIII [2]. These compounds exhibited hypoglycemic effects in a dose-dependent manner in streptozotocin-diabetic mice but showed no effects on glucose uptake and insulin release, suggesting that the hypoglycemic mechanism may be due to inhibition of hepatic gluconeogenesis and/or glycogenolysis.
TL;DR: A review of the production of the economically important alkaloids in plant cell cultures shows that presently only berberine and sanguinarine are being produced, and it seems that compartmentation also plays a role in the regulation of alkaloid biosynthesis.
Abstract: hsmcr.-The culture ofplant cells on a large scale in bioreactors has been shown to be feasible. The price of a plant cell biotechnological product is mainly governed by the slow growth of plant cell cultures, making the depreciation costs of the bioreactor the major costdetermining factor. A review of the production of the economically important alkaloids in plant cell cultures shows that presently only berberine and sanguinarine are being produced. Important factors to be considered in connection with accumulation of alkaloids are biosynthetic rate, accumulation site, and catabolism. Recent studies in the field of the regulation of the biosynthesis of terpenoid indole alkaloids on the level of genes and enzymes are reviewed, showing that it is feasible to clone genes from secondary metabolism and express these in various other plants. Concerning storage, it seems that compartmentation also plays a role in the regulation of alkaloid biosynthesis. Furthermore, catabolism of terpenoid indole alkaloids in cell cultures is an important factor, at some point even equalling the rate of de novo biosynthesis. The ongoing studies on regulation of alkaloid biosynthesis might eventually lead to transgenic plants or plant cell cultures with an improved productivity of the desired compounds. This knowledge is also of interest in connection with studies on the role of secondary metabolism for plants, and may contribute to a better understanding of resistance of plants to diseases and various herbivores. Of all known natural products, about 20% (i.e., about 16,000) are classified as alkaloids. For many of these alkaloids biological activities have been reported, but presently only about 30 are commercialized (1). Most of these are medicines, but some are used as flavoring, poison, and model compounds for pharmacological studies. These alkaloids can be qualified as specialty chemicals, as their worldwide production volume is limited; alkaloids such as quinine and quinidine have a yearly production of 300-500 metric tons, ajmalicine about 3600 kg, and compounds like vinblastine and vincristine in the kilogram range only (2,3). The amounts of plant material needed for the extraction of these compounds are, compared to agricultural crops, very small. For the examples mentioned this is in the order of 5000-10,000 metric tons ofCinchonu bark for the extraction of quinine and quinidine and 200-300 tons of Catharanthus roseus roots for the production of ajmalicine. The value ofeach of the markets of the major alkaloids can be estimated to be in the range of several hundred million dollars (4). These specialty chemicals are now produced by extraction from plant material that is cultivated or sometimes even still collected in the wild. There are several problems connected with this production method. Variable quantities and qualities of the plant material, plants that need to grow several years before they are ready for harvesting (e.g., Cinchona bark), and over-collecting of endangered species (e.g., Taxus hev$olia)
TL;DR: Comparison of the alkaloid content of S. pierrei and Stephania erecta strongly suggested separate identities for the two plants, and cytotoxic and antimalarial activity was found.
Abstract: Biological evaluation of extracts prepared from the tubers of Stephania pierrei revealed cytotoxic and antimalarial activity. During the course of separation, two new aporphine alkaloids, (-)-asimilobine-2-O-beta-D-glucoside [2] and (-)-nordicentrine [8], in addition to twenty-one known isoquinoline alkaloids, were isolated. Each isolate was assessed for cytotoxic and antimalarial activities. It was found that the cytotoxicity of S. pierrei was mainly due to the presence of the aporphine alkaloids containing the 1,2-methylenedioxy group 3-10, whereas the antimalarial activity was attributed to the nonquaternary aporphine alkaloids 1, 3-10 and the tetrahydroprotoberberines possessing a phenolic functionality, 13-15, 18. None of the isolates showed a degree of selectivity comparable to that of antimalarial drugs such as chloroquine, quinine, mefloquine, and artemisinin. Comparison of the alkaloid content of S. pierrei and Stephania erecta strongly suggested separate identities for the two plants.
TL;DR: With leucettamine A identified as a pure LTB4 receptor antagonist, a new structure lead is presented to inflammation therapy.
Abstract: Three new imidazole alkaloids, leucettamines A [1] and B [2] and leucettamidine [3], have been isolated from the Palauan sponge Leucetta microraphis. Their structures were established on the basis of extensive spectral analyses. Leucettamine A showed potent leukotriene B4 receptor binding activity (K(i) = 1.3 microM), while leucettamine B was essentially inactive (K(i) = 100 microM) and leucettamidine showed significant activity (K(i) = 5.3 microM). With leucettamine A identified as a pure LTB4 receptor antagonist, a new structure lead is presented to inflammation therapy.
TL;DR: Four pentacyclic guanidine derivatives related to ptilomycalin A have been isolated from the Mediterranean sponge Crambe crambe and were found to have a potent Ca++ antagonist effect and to inhibit the acetylcholine-induced contraction of guinea pig ileum at very low concentrations.
Abstract: Four pentacyclic guanidine derivatives (crambescidin 800 [5], crambescidin 816 [6], isocrambescidin 800 [9], and crambine [10]) related to ptilomycalin A [11] have been isolated from the Mediterranean sponge Crambe crambe. Isocrambescidin 800 and crambidine are new derivatives, the structures of which have been determined on the basis of their spectral properties. The absolute configuration of crambescidin 816 at the stereogenic center C-43 has been determined by applying Mosher's method. Pharmacological and biological activities of the Crambe crambe alkaloids are reported. In particular, crambescidin 816 was found to have a potent Ca++ antagonist effect and to inhibit the acetylcholine-induced contraction of guinea pig ileum at very low concentrations.
TL;DR: Skins of bufonid toads of the genus Melanophryniscus contain several classes of alkaloids, including precoccinelline [193A] and alkaloid 236, an oxime methyl ether, which are present in one population of Melanophile toads stelzneri.
Abstract: Skins of bufonid toads of the genus Melanophryniscus contain several classes of alkaloids: decahydroquinolines, pumiliotoxins, allopumiliotoxins, homopumiliotoxins, both 3,5- and 5,8-disubstituted indolizidines, 3,5-disubstituted pyrrolizidines, and a 1,4-disubstituted quinolizidine. Tricyclic alkaloids, including precoccinelline [193A] and alkaloid 236, an oxime methyl ether, are present in one population of Melanophryniscus stelzneri.
TL;DR: Twenty-four metabolites derived from marine sponges were evaluated for their cytotoxicities against two human tumor cell lines, non-small cell lung carcinoma A549 and colon adenocarcinoma HT-29, and against one murine leukemia cell line, P-388, and evaluation for their ability to effect signal transduction in a newly developed cell adhesion assay using an EL-4 cell line.
Abstract: Twenty-four metabolites derived from marine sponges were evaluated for their cytotoxicities against two human tumor cell lines, non-small cell lung carcinoma A549 and colon adenocarcinoma HT-29, and against one murine leukemia cell line, P-388, and evaluated for their ability to effect signal transduction in a newly developed cell adhesion assay using an EL-4 cell line. The compounds included latrunculin A [1], batzelline A [2], chondrillin [3], aureol [4], epihippuristanol, theonellamine B, discorhabdins A and C, kabiramide C, dercitin, meridine, manzamines A, B, and C, 8,15-diisocyano-11(20)-amphilectene and the corresponding C-15 formamide, a 20-carbon acetylenic alcohol, 4,5-dihydro-6"-deoxybromotopsentin, epispongiadiol, isospongiadiol, puupehenone, reiswigin A, and demethyl- and demethyloxyaaptamine. Latrunculin A [1], batzelline A [2], chondrillin [3], and aureol [4] expressed the desired profile of a greater than five-fold level of cytotoxicity against A549 relative to P-388, and an effect in the cell adhesion assay. In this group of compounds, cytotoxicity toward A549 was equal to or more pronounced than against HT-29. Latrunculin A was evaluated in an sc-implanted human A549 lung tumor xenograft mouse model and yielded a T/C of 146%. Batzelline A was evaluated in the cancer cell line panel at the National Cancer Institute and found to express selective cytotoxicity against several melanoma cancer cell lines.
TL;DR: A chemical screening protocol, utilizing various solid-phase extraction cartridges, has been developed for a second-stage dereplication and to assist in prioritization of these extracts for further investigations.
Abstract: A relatively high percentage (ca. 15%) of aqueous extracts from terrestrial plants, cyanobacteria, and marine invertebrates and algae has exhibited activity in the National Cancer Institute's primary AIDS-antiviral screen. By removal of anionic polysaccharides in a first stage of dereplication, we have eliminated from further consideration a considerable number of these extracts. However, a still substantial proportion of the active extracts remained, from which we wished to select and prioritize a small percentage for our detailed bioassay-directed fractionation studies. Therefore, a chemical screening protocol, utilizing various solid-phase extraction cartridges, has been developed for a second-stage dereplication and to assist in prioritization of these extracts for our further investigations.
TL;DR: The allelopathic potential of Ipomoea tricolor (Convolvulaceae), used in Mexican traditional agriculture as a weed controller, has been demonstrated by measuring the inhibitory activity of organic extracts on seedling growth of Amaranthus leucocarpus and Echinochloa crus-galli.
Abstract: The allelopathic potential of Ipomoea tricolor (Convolvulaceae), used in Mexican traditional agriculture as a weed controller, has been demonstrated by measuring the inhibitory activity of organic extracts on seedling growth of Amaranthus leucocarpus and Echinochloa crus-galli. Bioactivity-directed fractionation of the active CHCl3 extract led to the isolation of the allelopathic principle, which turned out to be a mixture of the so-called "resin glycosides" of convolvulaceous plants. The structure of tricolorin A, the major phytogrowth inhibitor present in the active fraction, was elucidated as (11S)-hydroxyhexadecanoic acid 11-O-alpha-L-rhamnopyranosyl-(1-->3)-O-alpha-L-[2-O-(2S-methylbutyryl)-4 -O- (2S-methylbutyryl)] rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->2)-beta-D-fucopyran oside- (1,3"-lactone)[1], based on chemical methods and spectral analysis including 1H-1H COSY, 1H-13CHETCOR, long range 1H-13C COLOC, and selective INEPT experiments. Bioassays showed that radicle elongation of the two weed seedlings tested was inhibited by tricolorin A [1] with IC50 values ranging from 12 to 37 microM. Staphylococcus aureus was sensitive to compound 1 with an MIC value of 1.8 micrograms/ml. Significant cytotoxic activity against cultured P-388 and human breast cancer cells (ED50 2.2 micrograms/ml) was demonstrated for compound 1, and it also inhibited phorbol 12,13-dibutyrate binding using calf brain homogenate as a source of protein kinase C (IC50 43 microM).
TL;DR: Through the concerted application of a series of homonuclear and inverse-detected 2D nmr experiments, the structure of the second alkaloid was established as a spiro-nonacyclic alkaloids, cryptospirolepine, which has been shown to have an empirical formula of C 34 H 24 N 4 O.
Abstract: From the alkaloidal fractions of the West African plant Cryptolepis sanguinolenta (Asclepiadaceae), two alkaloids were purified: one was identified as the known indoloquinoline alkaloid cryptolepine [1]. A second, novel alkaloid has shown to have an empirical formula of C 34 H 24 N 4 O based on exact mass measurement. Through the concerted application of a series of homonuclear and inverse-detected 2D nmr experiments, the structure of the second alkaloid was established as a spiro-nonacyclic alkaloid, cryptospirolepine
TL;DR: Antimicrobial activity of a number of East African plants was evaluated and plants collected based on information provided by medicine men showed a much higher probability of finding active extracts than the plants collected randomly.
Abstract: Antimicrobial activity of a number of East African plants was evaluated. The plants collected based on information provided by medicine men showed a much higher probability of finding active extracts than the plants collected randomly.
TL;DR: By bioactivity-directed fractionation, three new antimicrobial and cytotoxic 5,6-dihydro-alpha-pyrones, pectinolides A-C, have been isolated from Hyptis pect inata (Lamiaceae.
Abstract: By bioactivity-directed fractionation, three new antimicrobial and cytotoxic 5,6-dihydro-alpha-pyrones, pectinolides A-C, have been isolated from Hyptis pectinata (Lamiaceae). The absolute stereochemistry of pectinolide A [1] was established as 6S-[(3S-acetyloxy)-1Z-heptenyl]-5S-(acetyloxy)-5 ,6-dihydro-2H-pyran-2-one, on the basis of spectral, chiroptical, and chemical evidence. The structures of pectinolides B [2] and C [3] were determined as the monodeacetylated forms of 1 by comparison of their spectral data and chemical correlation with the prototype compound. Staphylococcus aureus and Bacillus subtilis were sensitive to pectinolide A [1] in the concentration range of 6.25-12.5 micrograms/ml. Compounds 1-3 exhibited significant cytotoxic activity (ED50 < 4 micrograms/ml) against a variety of tumor cell lines.
TL;DR: Analysis of skin alkaloids of seven different species of Mantella shows a new alkaloid class, which appears to contain a quinolizidine moiety, is seen in M. aurantiaca and M. crocea and is represented by 235C and several congeners.
Abstract: Brightly colored ranid frogs of the genus Mantella are found only in rain forests of Madagascar. Gc-ms and gc-Ft-ir analyses of skin alkaloids of seven different species, including four populations of Mantella madagascariensis, are reported. All contain one or more representatives of the pumiliotoxin A (PTX-A) class with the 13,14-dihydro derivatives 309A and 325A found in major amounts in the four populations of M. madagascariensis, while 307A (PTX-A) is found in two populations of M. madagascariensis and in three additional species, Mantella aurantiaca, Mantella viridis, and Mantella crocea. The latter three species also contain appreciable quantities of 323A (PTX-B). The four populations of M. madagascariensis show major amounts of two 1,4-disubstituted quinolizidines, 217A and 231A, and a 5,8-disubstituted indolizidine, 217B, in addition to many minor or trace quinolizidines and indolizidines. Such disubstituted quinolizidines and indolizidines are present as trace alkaloids in the six other species of Mantella, along with 3,5-disubstituted indolizidines, 3,5-disubstituted pyrrolizidines, the decahydroquinoline cis-195A, tricyclic alkaloids, and homopumiliotoxins. A new alkaloid class, which appears to contain a quinolizidine moiety, is seen in M. aurantiaca and M. crocea and is represented by 235C and several congeners.
TL;DR: A new cytotoxic arylnaphthalene lignan has been isolated from the Mexican medicinal plant Hyptis verticillata and characterized as 5-methoxydehydropodophyllotoxin, and the antimitotic potential of these compounds was determined in the astrocytoma (ASK) assay.
Abstract: A new cytotoxic (P-388 ED50 4 microgm/ml) arylnaphthalene lignan has been isolated from the Mexican medicinal plant Hyptis verticillata (Lamiaceae) and characterized as 5-methoxydehydropodophyllotoxin [1]. Eight additional lignans were also obtained by bioactivity-directed fractionation using the brine shrimp lethality test. Of these, the dehydro-beta-peltatin methyl ether 2 (P-388 ED50 1.8 microgm/ml) is reported for the first time as a natural product isolate. The other bioactive compounds were identified as dehydropodophyllotoxin [3], deoxydehydropodophyllotoxin [4]. (--)-yatein [5], 4'-demethyldeoxypodophyllotixin [6], isodeoxypodophyllotoxin [7], deoxypicropodophyllin [8], and beta-apopicropodophyllin [9]. Each of these compounds was evaluated against a panel of cell lines comprising a number of human cancer cell types [breast, colon, fibrosarcoma, lung, prostate, KB, and KB-VI (a multi-drug resistant cell line derived from KB)] and murine lymphocytic leukemia (P-388). Lignans 1-4 showed marginal cytotoxic activity against the human cell lines tested. In contrast, compounds 5-9 demonstrated a general nonspecific activity comparable to that of podophyllotoxin [12] (ED50 < 10-2 microgm/ml). In addition, the antimitotic potential of these compounds was determined in the astrocytoma (ASK) assay. Finally, the plant was also shown to contain the flavonoid sideritoflavone (KB ED50 1.6 microgm/ml) and the known pentacyclic triterpenoids ursolic, maslinic, 2 alpha-hydroxyursolic and oleanolic acids.
TL;DR: Compound 1 was found to show anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 3 micrograms/ml and the structure has been characterized as 24-methylenelanost-7,9(11)-diene-3 beta, 15 alpha-diol (suberosol) based on spectroscopic evidence.
Abstract: A new C31 lanostane-type triterpene, assigned the trivial name suberosol [1], has been isolated from Polyalthia suberosa as an anti-HIV principle. The structure has been characterized as 24-methylenelanost-7,9(11)-diene-3 beta, 15 alpha-diol (suberosol) [1], based on spectroscopic evidence. Compound 1 was found to show anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 3 micrograms/ml.
TL;DR: An alkaloid extract derived from the roots of Cyclea barbata demonstrated cytotoxic and antimalarial activities, and five bisbenzylisoquinoline alkaloids, (+)-tetrandrine, (-)-limacine, (+-thalrugosine), (+)-homoaromoline, and (-)-cycleapeltine were isolated as the active principles.
Abstract: An alkaloid extract derived from the roots of Cyclea barbata demonstrated cytotoxic and antimalarial activities, and five bisbenzylisoquinoline alkaloids, (+)-tetrandrine [1], (-)-limacine [2], (+)-thalrugosine [3], (+)-homoaromoline [4], and (-)-cycleapeltine [5], were isolated as the active principles. The complete and unambiguous assignments of the 1H- and 13C-nmr data of these substances were made by 1D and 2D nmr techniques (COSY, phase-sensitive ROESY, HETCOR, and FLOCK).
TL;DR: Petroleum ether and CHCl 3 extracts of stem, root bark, and leaves of Galipea longiflora were found active in vitro against Leishmania sp.
Abstract: Petroleum ether and CHCl 3 extracts of stem, root bark, and leaves of Galipea longiflora were found active in vitro against Leishmania sp. and Trypanosoma cruzi at 100 μg/ml. The activity-guided fractionation of the extracts by chromatography afforded thirteen active compounds identified as 2-substituted quinoline alkaloids. Four new 2-alkylquinoline alkaloids were isolated and identified from leaves of trunk bark of G. longiflora: 4-methoxy-2-n-propylquinoline {10} (chimanine A), 2-(E)-prop-1'-enylquinoline {11} (chimanine B), 4-methoxy-2-(E)-prop-1'-enylquinoline {12} (chimanine C), and 2-(1',2'-trans-epoxypropyl)-quinoline {13} (chimanine D)
TL;DR: In order to find new effective HIV protease inhibitors, two diterpenes were isolated from rosemary and carnosol showed the strongest inhibitory effect and did not inhibit cellular aspartic proteases cathepsin D and pepsin at the concentration range up to 10 micrograms/ml.
Abstract: In order to find new effective HIV protease inhibitors, two diterpenes (carnosic acid [1] and carnosol [5]) were isolated from rosemary (Rosmarinus officinalis L.), and rosmanol [2] and semisynthetic derivatives (7-O-methylrosmanol [3], 7-O-ethylrosmanol [4], and 11,12-O,O-dimethylcarnosol [6]) were prepared. The inhibitory activity of all six compounds against HIV-1 protease was tested. The carnosic acid [1] showed the strongest inhibitory effect (IC90 = 0.08 micrograms/ml). The same compound was also assayed against HIV-1 virus replication (IC90 = 0.32 micrograms/ml). The cytotoxic TC90 on H9 lymphocytes was 0.36 micrograms/ml, which is very close to the effective antiviral dose. Additionally, the tested compounds did not inhibit cellular aspartic proteases cathepsin D and pepsin at the concentration range up to 10 micrograms/ml [corrected].
TL;DR: In this article, two new diol alpha-methylene lactone antimicrobial agents were identified from nmr and mass spectral data and X-ray crystallography as (4 alpha, 5 alpha, 8 beta, 10 beta)-4,10-dihydroxyl-1,11 (13)-guaidien-12,8-olide, which differ in stereochemistry at the C-10 tertiary alcohol center.
Abstract: Extracts of the plant Jasonia candicans possess antimicrobial activity. ET2O/MeOH extracts were subjected to liquid chromatography, and several sesquiterpenes were isolated and identified including the known compounds confertin [1], 4,11(13)-eudesmadien-12-oic acid [2], and 11-eudesmen-4-ol [3]. Two new diol alpha-methylene lactone antimicrobial agents were identified from nmr and mass spectral data and X-ray crystallography as (4 alpha, 5 alpha, 8 beta, 10 beta)-4,10-dihydroxy-1,11(13)-guaidien-12,8-olide [4] and (4 alpha, 5 alpha, 8 beta, 10 alpha)-4,10-dihydroxyl-1,11 (13)-guaidien-12,8-olide[5], which differ in stereochemistry at the C-10 tertiary alcohol center.