During an ethnopharmacological survey of antiparasitic medicinal plants used in Ivory Coast, 17 plants were identified and collected. Polar, non-polar and alkaloidic extracts of various parts of these species were evaluated in vitro in an antiparasitic drug screening. Antimalarial, leishmanicidal, trypanocidal, antihelminthiasis and antiscabies activities were determined. Among the selected plants, Anogeissus leiocarpus and Terminalia glaucescens were strongly active against Plasmodium falciparum. Lawsonia inermis, selectively prescribed against trypanosomiasis shows interesting trypanocidal activities as did other 15 plants. Anthelmintic activities were found for 10 active species and 2 species (Uvaria afzelli and Monodora myristica) were actives against mites.

The urgency generated by drug-resistant strains of malaria has accelerated anti-malarial drug research over the last two decades. While synthetic pharmaceutical agents continue to dominate research, attention increasingly has been directed to natural products. The present paper explores the larger context in which plant use occurs and considers how the selection of medicinal plants has evolved over millennia as part of the larger human effort to mediate illness. First attention is directed to indigenous medicinal plants whose anti-malarial activity is based on an oxidant mode of action, by which intracellular constituents lose electrons (become more electropositive). Next, parallels are drawn between these plant substances and a suite of malaria-protective genetic traits: glucose-6-phosphate dehydrogenase deficiency; haemoglobins S, C and E; alpha- and beta-thalassemias. These erythrocyte anomalies are classic examples of Darwinian evolution, occurring in high frequency in populations who have experienced considerable selective pressure from malaria. Characterized by discrete loci and pathophysiologies, they are united through the phenomenon of increased erythrocyte oxidation. In this model, then, oxidant anti-malarial plants are culturally constructed analogues, and molecular mimics, of these genetic adaptations. To further reinforce the scheme, it is noted that the anti-malarial action of pharmaceutical agents such as chloroquine and mefloquine duplicates both the genetic anomalies and the folk therapeutic models based in oxidant plants. This discussion coheres around a theoretical foundation that relates plant secondary metabolites (oxidants) to plasmodial biochemistry and human biological and cultural adaptations to malaria. Co-evolution provides a theoretical link that illuminates how medical cultures manage the relationships among humans, plants, herbivores and their respective pathogens.

Parasitic diseases caused by protozoa as Leishmania, Trypanosome or Plasmodium are responsible for more than three millions deaths annually throughout the developing countries. This review covers recent studies on plant-secondary metabolites isolated from medicinal plants and that have demonstrated moderate to high activity in in vitro and in vivo bioassays against these protozoa. The biological activity of the last promising antiparasitic leads are described.

Three Uvaria species, namely U. klaineana, U. mocoli and U. versicolor were tested in vitro against Dermatophagoides pteronyssinus, the European house dust mite. The most active extracts were the Uvaria versicolor stems crude methanol and hexane extracts with EC(50) values of 0.095 g/m(2 )and 0.12 g/m(2), respectively. The bioassay-guided fractionation of the hexane extract led to the isolation of benzyl benzoate (1). which exhibited an EC(50) value of 0.045 g/m(2). A new fl avanone, versuvanone (2). and the known oxoaporphine liriodenine (3). were also isolated from this species and showed EC(50) values > 1.5 g/m(2). A weak acaricidal activity (0.85 g/m(2)) was observed for the dichloromethane extract of Uvaria klaineana, due to the presence of benzyl benzoate. Uvaria mocoli was inactive. The structures of compounds were elucidated using 2D-NMR techniques.

During an ethnopharmacological survey of antiparasitic medicinal plants used in Ivory Coast, 17 plants were identified and collected. Polar, non-polar and alkaloidic extracts of various parts of these species were evaluated in vitro in an antiparasitic drug screening. Antimalarial, leishmanicidal, trypanocidal, antihelminthiasis and antiscabies activities were determined. Among the selected plants, Anogeissus leiocarpus and Terminalia glaucescens were strongly active against Plasmodium falciparum. Lawsonia inermis, selectively prescribed against trypanosomiasis shows interesting trypanocidal activities as did other 15 plants. Anthelmintic activities were found for 10 active species and 2 species (Uvaria afzelli and Monodora myristica) were actives against mites.

The active compounds obtained from some medicinal plants used traditionally worldwide for the treatment of leishmaniasis are reviewed. Among these active molecules, described in recent literature are quinoline alkaloids such as alkyl-2 quinoline and aryl-2 quinoline from Galipea longiflora, isoquinoline alkaloids such as isoguattouregidine from Guatteria foliosa, indole alkaloids such as conodurine and gabunine from Pescheiera van heurkii, terpenes such as jatrogrossidione from Jatropha grossidentata, acetogenins such as senegalene from Annona senegalensis and lignans such as (+)nyasol from Asparagus africanus. Other natural compounds with antileishmanial activity are coumarins, chalcones, lactones, tetralones and saponins. Some of them are known antiprotozoal natural products. These compounds could be used as templates to discover new and effective drugs against leishmaniasis.

A novel acetogenin, coronin, was isolated from the roots of Annona muricata L. The structure was elucidated by a combination of chemical and spectral methods including MS and NMR measurements. Coronin is probably an intermediate in the biosynthetic pathway of bis-tetrahydrofuran acetogenins, and is proposed as a biogenetic precursor of neoannonin-B.

Three new bistetrahydrofuran acetogenins, carolins A-C (1-3), were isolated from the MeOH extract of Annona spinescens in addition to the known compound, squamocin (4). The structures of 1, 2, and 3 were elucidated by spectroscopic methods including LSIMS/MS technique and confirmed by a chemical transformation, The cytotoxic activity of the new compounds 1-3 is reported and discussed in comparison with 4 and the previously isolated spinencin (5).

Bioactivity-guided fractionations of chloromethylenic extract of the roots of U. afzelii (Annonaceae), using Leishmania donovani and Trypanosoma brucei brucei bioassay, resulted in the isolation of the two known compounds, emorydone (1) and demethoxymatteucinol (2), previously isolated from the stems, which were characterised from this source. In addition, the novel 1-indanone, afzeliindanone (3), was also isolated. The structure determination of afzeliindanone (3) was elucidated on the basis of spectral data as 4-[4-hydroxy-3-methoxyphenyl]-indan-1-one. This compound is the first 1-indanone derivative isolated from plants.

Annonaceae is a large family of plants widely used in alimentation and traditional medicine. The interest of their study is raised up by the presence of biologically active substances among that the acetogenins which are specific to them. In Senegal, three species are widely used in traditional medicine for various indications and particularly in parasitic diseases: Annona senegalensis, Uvaria chamae and Xylopia aethiopica. The study of antiparasitical extracts from various organs showed an interesting activity of the fruits and leaves of Xylopia aethiopica on Leishmania donovani, the stem barks and roots of Uvaria chamae on Trypanosomia brucei and the roots of Annona senegalensis on the chloroquino-resistant strain of Plasmodium falciparum. Bioguided fractionation of the active extracts led to isolate Annonaceous acetogenins. Therefore, thirteen acetogenins, from the roots of Uvaria chamae and Annona senegalensis, were identified. The presence of acetogenins, substances with antiparasitical activity, could partly explain the biological proprieties of these various drugs.

Twelve acetogenins from Annonaceae were evaluated in vitro for their antileishmanial activities in order to search for new lead-compounds having antileishmanial properties. The compounds were comparatively evaluated by the 50% inhibitory concentrations (IC50) determination on promastigote forms of wild-type and four drug-resistant lines of Leishmania donovani. In addition, after testing the toxicity on mouse peritoneal macrophages, the compounds were evaluated on amastigote infected macrophages and a therapeutic index was calculated. The IC50 of the acetogenins against promastigote forms of L. donovani was in a range 4.7-47.3 microM. The most active compound was Rolliniastatin 1 (IC50 at 4.7 microM). On the intramacrophage amastigote in vitro model, only seven compounds exhibited measurable antileishmanial activity with IC50 values in a range 2.5-29.7 microM. Rollinistatin 1 was the most interesting compound with IC50 of 2.5 microM and it appears as the most promising one on the basis of therapeutic index (18.08). Isoannonacin, which is active against intramacrophagic amastigotes (IC50 of 6.2 microM) with a therapeutic index of 2.05, exhibited a strong action on drug-resistant strains (IC50 from 5.1 to 9.8 microM). Acetogenins are a new chemical series with interesting in vitro antileishmanial activity and further studies will be focused on the understanding of this selectivity in regard to the membrane and mitochondrial action using specific probes.

The death of dopaminergic neurons induced by systemic administration of mitochondrial respiratory chain complex I inhibitors such as 1-methyl-4-phenylpyridinium (MPP(+); given as the prodrug 1-methyl-1,2,3,6-tetrahydropyridine) or the pesticide rotenone have raised the question as to whether this family of compounds are the cause of some forms of Parkinsonism. We have examined the neurotoxic potential of another complex I inhibitor, annonacin, the major acetogenin of Annona muricata (soursop), a tropical plant suspected to be the cause of an atypical form of Parkinson disease in the French West Indies (Guadeloupe). When added to mesencephalic cultures for 24 h, annonacin was much more potent than MPP(+)(effective concentration [EC(50)]=0.018 versus 1.9 microM) and as effective as rotenone (EC(50)=0.034 microM) in killing dopaminergic neurons. The uptake of [(3)H]-dopamine used as an index of dopaminergic cell function was similarly reduced. Toxic effects were seen at lower concentrations when the incubation time was extended by several days whereas withdrawal of the toxin after a short-term exposure (<6 h) arrested cell demise. Unlike MPP(+) but similar to rotenone, the acetogenin also reduced the survival of non-dopaminergic neurons. Neuronal cell death was not excitotoxic and occurred independently of free radical production. Raising the concentrations of either glucose or mannose in the presence of annonacin restored to a large extent intracellular ATP synthesis and prevented neuronal cell demise. Deoxyglucose reversed the effects of both glucose and mannose. Other hexoses such as galactose and fructose were not protective. Attempts to restore oxidative phosphorylation with lactate or pyruvate failed to provide protection to dopaminergic neurons whereas idoacetate, an inhibitor of glycolysis, inhibited the survival promoting effects of glucose and mannose indicating that these two hexoses acted independently of mitochondria by stimulating glycolysis. In conclusion, our study demonstrates that annonacin promotes dopaminergic neuronal death by impairment of energy production. It also underlines the need to address its possible role in the etiology of some atypical forms of Parkinsonism in Guadeloupe.

The acetone extract of the root bark of Erythrina burttii showed in vitro antiplasmodial activity against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC(50) values of 0.97 ± 0.2 and 1.73 ± 0.5 μg/ml respectively. The extract also had radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical with an EC(50) value of 12.0 μg/ml. The isoflav-3-enes burttinol-A and burttinol-C, and the 2-arylbenzofuran derivative burttinol-D were identified as the most active antiplasmodial (IC(50)<10 μM) and free radical scavenging (EC(50)ca. 10 μM) principles. The acetone extract of E. burttii at 800 mg/kg/day, in a 4-day Plasmodium berghei ANKA suppressive test, showed in vivo antimalarial activity with 52% chemosuppression. In the same in vivo test, marginal activities were also observed for the extracts of the root and stem bark of Erythrina abyssinica and the root bark of Erythrina sacleuxii.

Stephania rotunda (Menispermaceae), a creeper commonly found in the mountainous areas of Cambodia, has been mainly used for the treatment of fever and malaria. Thus, the aim of this study is to investigate the chemical composition and antiplasmodial activity of different samples of S. rotunda and compare their antiplasmodial activity with their alkaloid content. Sixteen samples from different parts (roots, stem, and tuber) of S. rotunda were collected from four regions of Cambodia (Battambang, Pailin, Siem Reap, and Kampot). Reversed-phase HPLC was used to determine the content of three bioactive alkaloids (cepharanthine, tetrahydropalmatine, and xylopinine). These three alkaloids have been found in all samples from Battambang and Pailin (samples I-IX), whereas only tetrahydropalmatine was present in samples from Siem Reap and Kampot (samples X-XVI). The analyzed extracts were evaluated for their antiplasmodial activity on W2 strain of Plasmodium falciparum. Among them, 13 extracts were significantly active with inhibitory concentration 50 (IC(50)) from 1.2 to 3.7 µg/mL and 2 extracts were moderately active (IC(50)  = 6.1 and 10 µg/mL, respectively), whereas sample XI was not active (IC(50)  = 19.6 µg/mL). A comparison between antiplasmodial activity and concentration of the three bioactive alkaloids in S. rotunda extracts has been realized. Copyright © 2012 John Wiley & Sons, Ltd.

Bioassay-guided fractionation of the MeOH extract from the stem bark of Neonauclea purpurea used in traditional medicine, resulted in the isolation of 2 indole alkaloids, cadambine (1) and alpha-dihydrocadambine (2), as well as a quinolic compound, 2,6-dimethoxy-1,4-benzoquinone (3). Antimalarial activity evaluation showed that compounds 2 and 3 exhibited mild in vitro antimalarial activity against Plasmodium falciparum, the chloroquine-resistant strain K1 with IC50 values of 6.6 and 11.3 microM, respectively. Compounds 1 and 2 showed no cytotoxicity to monkey (Vero) cells, but compound 3 showed weak cytotoxicity with an IC50 value of 1.19 microM.

AIM This study was designed for isolating and characterizing antiplasmodial compounds from marine octocoral-associated bacteria. MATERIALS AND METHODS The organic extract of the Bacillus sp. was subjected to purification using several chromatography techniques guided by bioassays to yield three isocoumarin derivatives (1-3). Chemical structures of the compounds were elucidated on the basis of HRMS spectra and NMR spectroscopy. The antiplasmodial activity of the isolated compounds was evaluated in vitro against the chloroquine-resistant Plasmodium falciparum strain W2. RESULTS Isolated compounds were identified as bacilosarcin A (1), AI77-F (2), and AI77-H (3). Bacilosarcin A (1) displayed a low micromolar activity (IC(50)= 2.2 μM) against P. falciparum while compounds 2 and 3 showed no activity. CONCLUSIONS Bacilosarcin A was found to be responsible for the antiplasmodial activity observed in the crude extract obtained from the Bacillus sp.

Four new alkaloids, cassiarins G, H, J, and K (1-4) which showed moderate antiplasmodial activity against Plasmodium falciparum 3D7, were isolated from the leaves of Cassia siamea (Leguminosae) and the structures of 1-4 were elucidated by 1D- and 2D-NMR analysis and X-ray crystallographic analysis.

We investigated the antiplasmodial properties of crude extracts from Carica papaya leaves to trace the activity through bioassay-guided fractionation. The greatest antiplasmodial activity was observed in the ethyl acetate crude extract. C. papaya showed a high selectivity for P. falciparum against CHO cells with a selectivity index of 249.25 and 185.37 in the chloroquine-sensitive D10 and chloroquine-resistant DD2 strains, respectively. Carica papaya ethyl acetate extract was subjected to bioassay-guided fractionation to ascertain the most active fraction, which was purified and identified using high-pressure liquid chromatography (HPLC) and GC-MS (Gas chromatography-Mass spectrometry) methods. Linoleic and linolenic acids identified from the ethyl acetate fraction showed IC(50) of 6.88 μg/ml and 3.58 μg/ml, respectively. The study demonstrated greater antiplasmodial activity of the crude ethyl acetate extract of Carica papaya leaves with an IC(50) of 2.96 ± 0.14 μg/ml when compared to the activity of the fractions and isolated compounds.

The chemical composition of the aerial parts of the Cape Verdean endemic shrub Artemisia gorgonum Webb (Asteraceae) was careful investigated, which led to the isolation and identification of six known furfuran lignans: eudesmin (1), magnolin (2), epimagnolin A (3), aschantin (4), kobusin (5), sesamin (6) and a flavone: artemetin (7). Compounds 1-7 were evaluated in vitro for their cytotoxicity in a screening panel consisting of various mammalian tumor cell lines, for their antimalarial activity against chloroquine-resistant Plasmodium falciparum (FcB1 strain) and for their cytotoxicity against murine normal cells (CFU-GM). While no promising cytotoxicity against human tumor cells were noticed, marginal potency and selectivity was found for compounds 1-5 against murine colon 38. Besides, compounds 2-7 showed mild antiplasmodial activities, 6 and 7 being the most active compounds (IC(50) 3.37 and 3.50 μg/ml respectively) without noticeable toxicity on mammalian normal cells. This is the first report of antiplasmodial activity for furfuran lignans and the first isolation of 1-7 from Artemisia gorgonum.

The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50)= 0.9-3 µg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50)= 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three--nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.

In the course of our investigations on Strychnos usambarensis leaves in order to isolate isostrychnopentamine, the main alkaloid responsible for the antiplasmodial activity of the plant, a new tertiary indolic alkaloid has been isolated: 17-O-acetyl,10-hydroxycorynantheol 1. Its structure was determined by means of spectroscopic and spectrometric methods such as UV, IR, CD, NMR, and ESI-MS. 17-O-acetyl,10-hydroxycorynantheol 1 is one of the most active monomeric indole alkaloids known to date showing an in vitro activity against Plasmodium falciparum close to 5 µM and a high selectivity.

New 4-aminoquinoline-derived esters containing the redox-active ferrocene group brought in by either ferrocenyformic or 4-ferrocenylbutanoic acids were synthesized and tested in vitro for their antiplasmodial activity. The results revealed that only esters derived from ferrocenylformic acid were active against both chloroquine (CQ)-resistant Dd2 and CQ-sensitive D10 strains of Plasmodium falciparum. However, none of these showed higher actvity than CQ against the sensitive strain. Ester 16, which possesses a butyl branch in the structure, was the most active of all. With an IC50 of 0.13 mM on the resistant strain, this ester possessed 2.5-fold higher activity than CQ (IC50 = 0.34 mM). All tested esters showed good selectivity towards P. falciparum with indexes higher than 60.