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Biomedical subjects

J D Phillipson

Publications and source records attributed to J D Phillipson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bio-active compounds from Psychotria camponutans.

A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have been isolated from the woody parts of Psychotria camponutans, as a result of bioactivity-guided fractionation. The compounds were characterized by UV, IR, EI-mass, 1H-, and 13C-NMR, and HETCOR NMR spectroscopy. Both compounds, together with acetylbenzoisochromanquinone, showed in vitro strong activity against brine shrimp, KB cells, and chloroquine-resistant P. falciparum.

Animals↗
PubMed1994

Natural products as drugs.

Higher plants, many of which are threatened with extinction, are used as sources of pharmaceuticals and as ingredients of traditional medicines and are of value in new drug discovery. Artemisinin, taxol and camptothecin are examples of natural products which are undergoing clinical and commercial development. Several natural products isolated from plants used in traditional medicine have potent antiplasmodial action in vitro and represent potential sources of new antimalarial drugs. Plant biotechnology offers the possibility of improved production methods of cultivated medicinal plants as well as alternative approaches to the production of natural products for the preparation of pharmaceuticals.

Antimalarials↗
PubMed1994

Studies on the anti-tumour, anti-bacterial, and wound-healing properties of dragon's blood.

Three in-vitro assays have been adopted to examine the cytotoxicity and anti-bacterial activity of the blood-red sap of Croton lechleri from Ecuador, and to examine its effect upon the proliferation of endothelial cells. The sap was found not to be cytotoxic. Several simple phenolic compounds and diterpenes showed a potent anti-bacterial activity. The sap has little effect upon the proliferation of endothelial cells, and no single active ingredient was identified. A mechanism for the wound-healing property of the sap has been proposed.

Animals↗
PubMed1994

In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of bisbenzylisoquinoline alkaloids.

Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal, antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50) of less than 1 microM against a multidrug-resistant strain of Plasmodium falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most active against Entamoeba histolytica, aromoline, isotrilobine, and insularine, had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids merit further investigation as potential novel antimalarial agents.

Alkaloids↗
PubMed1993

Proton NMR lipid profile of Leishmania donovani promastigotes.

The proton nuclear magnetic resonance (NMR) lipid profile of Leishmania donovani was obtained in the one-dimensional and two-dimensional modes. Partial assignments of lipid classes and individual lipids were obtained purely from the proton NMR spectrum of the mixture. A more complete assignment and quantitative analysis was achieved by prior separation of the lipids by high pressure liquid chromatography (HPLC) followed by proton NMR analysis of the fractions. This work showed that proton NMR spectroscopy could facilitate lipid analysis and classification of various parasitic protozoa and serve as a basis for rapid studies of comparative lipid metabolism in parasites.

Animals↗
PubMed1993

Alstonia species: are they effective in malaria treatment?

A review of the literature on Alstonia species indicates that evidence in support of their effectiveness in the treatment of malaria is controversial. The antiprotozoal activity of the major alkaloid present in Alstonia species, echitamine, was assessed in vitro against Plasmodium falciparum and Giardia intestinalis. Echitamine displayed little antiplasmodial activity, but two quinoline alkaloids from A. coriacea (corialstonine and corialstonidine) were found to have some activity against P. falciparum although this was approximately 10 times less than that of quinine. None of the three Alstonia alkaloids was active against G. intestinalis. These results are discussed in the context of previously published data.

Alkaloids↗
PubMed1993

Antimalarial activity from 'Mhekara' (Uapaca nitida Müll-Arg.), a Tanzanian tree.

An aqueous decoction of the root bark of Uapaca nitida Müll-Arg. is currently used locally at the Benedictine Mission at Peramiho in Tanzania to treat malaria. We have now demonstrated that extracts of root bark and leaves of this tree are active against the multidrug-resistant K1 strain of Plasmodium falciparum in vitro. An ethanolic extract of root bark showed activity against P. berghei in mice but at a dose which also showed toxic effects. The use of this plant in treating malaria appears to be novel and further studies would be of value.

Animals↗
PubMed1993

A microwell cytotoxicity assay using Artemia salina (brine shrimp).

A new microplate assay for cytotoxicity testing using A. salina has been developed and shown to give results comparable to a previously published test-tube method. The assay reliably detected all of the compounds toxic to KB cells in a series of 21 pharmacologically active agents, except for two which require metabolic activation in man. Four quassinoids with cytotoxic and antiplasmodial activity were also toxic to the brine shrimp while quassin itself was inactive in all three systems. It is proposed that this assay provides a convenient means by which the presence of cytotoxic quassinoids may be detected during the fractionation of plant extracts.

Animals↗
PubMed1992

Parasitological and microbiological evaluation of Mixe Indian medicinal plants (Mexico).

Medicinal plants are an important health resource in many regions of the Americas and are of particular importance to many Indian communities. Based on a recent ethnobotanical study in Mexico, we investigated the activity of 29 plant extracts against Entamoeba histolytica, three bacteria (Bacillus subtilis, Escherichia coli, and Micrococcus luteus) and two fungi (Cladosporium cucumerinum and Penicillium oxalicum). After separation of these extracts between CH2Cl2 and H2O the resulting phases were also evaluated.

Amebicides↗
PubMed1991

High-performance liquid chromatographic-mass spectrometric assay of high-value compounds for pharmaceutical use from plant cell tissue culture: Cinchona alkaloids.

The use of high-performance liquid chromatography (HPLC) interfaced with thermospray (TSP) mass spectrometry is described for the separation and identification of various alkaloids from Cinchona ledgeriana extracts. The use of water-acetonitrile-acetic acid (71:25:4) with 0.01 M ammonium acetate (pH 3.0) as the mobile phase gave good HPLC separation and good TSP sensitivity. The specificity obtained by single-ion monitoring allowed the analysis of commercially important alkaloids such as quinine and quinidine in plant material, transformed roots and in cells from tissue culture, with relatively simple extraction and work-up procedures. TSP gave protonated species with few fragment ions but collision-induced dissociation offers the promise of increased analytically specificity from the fragment ion data. This work has important implications for the biotechnological production of pharmaceuticals normally obtained from plant sources.

Chromatography, High Pressure Liquid↗
PubMed1991

Can ethnopharmacology contribute to the development of antimalarial agents?

The resistance of Plasmodium falciparum, the cause of tertian malaria, to synthetic antimalarials, together with the resistance of the vector mosquitoes to insecticides, has resulted in a resurgence in the use of quinine and a search for new antimalarial agents. In recent years, artemisinin, isolated from Artemisia annua which is used in Chinese traditional medicine for the treatment of malaria, has proved to be effective in the treatment of cerebral malaria due to chloroquine-resistant strains of P. falciparum. The development of in vitro tests utilising P. falciparum obtained from malaria patients means that it is possible to use bioassay guided fractionation of active extracts in order to isolate active principles. A number of laboratories throughout the world are currently investigating plants used in traditional medicine for their active constituents. Some of their results will be described and in particular two aspects of our investigations with species of Simaroubaceae and Menispermaceae will be discussed. There is every possibility that such approaches which use leads from Ethnopharmacology will result in the development of new antimalarial agents. It is vitally important to those populations relying on traditional medicines for the treatment of malaria that the safety and efficacy of such medicines be established, their active principles determined and that reproducible dosage forms be prepared and made available for use.

Animals↗
PubMed1991

In vitro cytotoxicity of a series of quassinoids from Brucea javanica fruits against KB cells.

A microdilution technique was developed for the assessment of in vitro cytotoxicity against KB cells derived from a human epidermoid carcinoma of the nasopharynx. The test was used to determine the cytotoxicity of a series of quassinoids, isolated from Brucea javanica, and which have previously been shown to demonstrate activity against Plasmodium falciparum. The 50% effective dose (ED50) for 7 quassinoids tested against KB ranged from 0.008 microgram/ml for bruceantin, the most cytotoxic of the compounds tested to greater than 5 micrograms/ml for bruceolide, the least toxic tested. The activities of the quassinoids against KB did not parallel the known activities of the quassinoids against Plasmodium falciparum suggesting that the quassinoid mode of antimalarial action is not a simple cytotoxic effect and lends support to further investigation of the structure activity relationships within this group of compounds.

Antimalarials↗
PubMed1991

Antiamoebic and antiplasmodial activities of alkaloids isolated from Strychnos usambarensis.

Seven alkaloids isolated from Strychnos usambarensis have been assessed for in vitro activities against Entamoeba histolytica and Plasmodium falciparum and for in vivo activity against Plasmodium berghei in mice. Strychnopentamine and 3',4'-dihydrousambarensine were highly active against P. falciparum in vitro, but were inactive and non-toxic against P. berghei in vivo. Usambarensine, usambarine, and 18,19-dihydrousambarine were highly active against E. histolytica in vitro, but were less active against P. falciparum in vitro. Nb-Methylusambarensine was less active against both protozoa than was usambarensine, and akagerine possessed little antiprotozoal activity. Structure-activity relationships are discussed in the context of the reported cytotoxic and pharmacological properties of these alkaloids.

Alkaloids↗
PubMed1991

Antiprotozoal agents from plant sources.

Protozoa are responsible for a number of serious tropical diseases including amoebiasis, leishmaniasis, malaria, and trypanosomiasis. New drugs are required for the treatment of these diseases and the potential of plants to produce new clinical agents is discussed.

Journal Article↗
PubMed1991

Plasmodium falciparum: effects of phaeanthine, a naturally-occurring bisbenzylisoquinoline alkaloid, on chloroquine-resistant and -sensitive parasites in vitro, and its influence on chloroquine activity.

Phaeanthine, a bisbenzylisoquinoline alkaloid which occurs naturally in Triclisia species, was extracted from Triclisia patens (Menispermaceae) obtained from Sierra Leone (West Africa). In vitro, phaeanthine was found to be twice as potent against a chloroquine-resistant Plasmodium falciparum strain (K1), as against a chloroquine-sensitive clone (T9-96), with 50% inhibitory concentrations of 365.85 (+/- 11.41) nM and 704.87 (+/- 81.48) nM respectively. At a sub-inhibitory concentration of 80.35 nM, chloroquine resistance was not reversed by phaeanthine. Isobolograms constructed from experiments with chloroquine/phaeanthine combinations showed antagonism in T9-96 and an additive effect in K1. In a 48-hour microtest, phaeanthine at antimalarial concentrations showed no cytotoxicity to mammalian (KB) cells in vitro.

Animals↗
PubMed1991

Antiprotozoal agents from plant sources.

Protozoa are responsible for a number of serious tropical diseases including amoebiasis, leishmaniasis, malaria, and trypanosomiasis. New drugs are required for the treatment of these diseases and the potential of plants to produce new clinical agents is discussed.

Antiprotozoal Agents↗
PubMed1990

Comparison of the in vitro activities of quassinoids with activity against Plasmodium falciparum, anisomycin and some other inhibitors of eukaryotic protein synthesis.

Using the inhibition of incorporation of [3H]hypoxanthine as an index of viability of malaria parasites, it was shown that a chloroquine-sensitive strain of Plasmodium falciparum (T9-96) and a chloroquine-resistant strain (K1) did not differ in their sensitivities to the quassinoids ailanthinone, bruceantin and chaparrin. Similarly, there were no differences between the strains in their sensitivities to the protein synthesis inhibitors anisomycin, deacetylanisomycin, cephalotaxine, homoharringtonine, cycloheximide, puromycin and puromycin aminonucleoside. The IC50 values derived for ailanthinone and bruceantin, cycloheximide, homoharringtonine and puromycin were in the nanomolar range, whereas those for the anisomycins, cephalotaxine and the aminonucleoside of puromycin were micromolar or greater. Those drugs tested which contain an ester moiety (ailanthinone, bruceantin, anisomycin, homoharringtonine) were more active than the related drugs (chaparrin, deacetylanisomycin, cephalotaxine) that do not. Cross-resistance to inhibitors of protein synthesis appeared not to accompany resistance to chloroquine.

Animals↗