Highest Antiplasmodial Activity Research Articles

Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound

BackgroundNatural products could play an important role in the challenge to discover new anti-malarial drugs. In a previous study, Dicoma tomentosa (Asteraceae) was selected for its promising anti-plasmodial activity after a preliminary screening of several plants traditionally used in Burkina Faso to treat malaria. The aim of the present study was to further investigate the anti-plasmodial properties of this plant and to isolate the active anti-plasmodial compounds.MethodsEight crude extracts obtained from D. tomentosa whole plant were tested in vitro against two Plasmodium falciparum strains (3D7 and W2) using the p-LDH assay (colorimetric method). The Peters’ four-days suppressive test model (Plasmodium berghei-infected mice) was used to evaluate the in vivo anti-plasmodial activity. An in vitro bioguided fractionation was undertaken on a dichloromethane extract, using preparative HPLC and TLC techniques. The identity of the pure compound was assessed using UV, MS and NMR spectroscopic analysis. In vitro cytotoxicity against WI38 human fibroblasts (WST-1 assay) and haemolytic activity were also evaluated for extracts and pure compounds in order to check selectivity.ResultsThe best in vitro anti-plasmodial results were obtained with the dichloromethane, diethylether, ethylacetate and methanol extracts, which exhibited a high activity (IC50 ≤ 5 μg/ml). Hot water and hydroethanolic extracts also showed a good activity (IC50 ≤ 15 μg/ml), which confirmed the traditional use and the promising anti-malarial potential of the plant. The activity was also confirmed in vivo for all tested extracts. However, most of the active extracts also exhibited cytotoxic activity, but no extract was found to display any haemolytic activity. The bioguided fractionation process allowed to isolate and identify a sesquiterpene lactone (urospermal A-15-O-acetate) as the major anti-plasmodial compound of the plant (IC50 < 1 μg/ml against both 3D7 and W2 strains). This was also found to be the main cytotoxic compound (SI = 3.3). While this melampolide has already been described in the plant, this paper is the first report on the biological properties of this compound.ConclusionsThe present study highlighted the very promising anti-plasmodial activity of D. tomentosa and enabled to identify its main active compound, urospermal A-15-O-acetate. The high anti-plasmodial activity of this compound merits further study about its anti-plasmodial mechanism of action. The active extracts of D. tomentosa, as well as urospermal A 15-O-acetate, displayed only a moderate selectivity, and further studies are needed to assess the safety of the use of the plant by the local population.

Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline

With the aim to investigate the effect of different heterocyclic rings linked to the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-aminoquinoline was synthesized and tested in vitro against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited from moderate to high antiplasmodial activities. The activity was strongly influenced both by the presence of a methylenic group, as a spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence of a basic head. The most potent molecules inhibited the growth of both CQ-S and CQ-R strains of P. falciparum with IC50<30nM and were not toxic against human endothelial cells. These results confirm that the presence of an heteroaryl moiety in the side chain of 7-chloro-4-aminoquinoline is useful for the design and development of new powerful antimalarial agents.

SYNTHESIS AND ANTIPLASMODIAL ACTIVITY TESTING OF (1)-N-ALKYL- AND (1)-N-BENZYL-6-NITRO-1,10-PHENANTHROLINIUM SALTS AS NEW POTENTIAL ANTIMALARIAL AGENTS

The synthesis of 5-nitro-1,10-phenanthroline hydrate 2 derivatives from 1,10-phenanthroline monohydrate as starting material has been carried out. The 5-nitro-1,10-phenanthroline hydrate 2 was obtained through nitration reaction using H2SO4 and HNO3 as catalyst and reagent, respectively. Synthesis of (1)-N-alkyl-6-nitro- and (1)-N-benzyl-6-nitro-1,10-phenanthrolinium have been prepared using dimethyl sulphate (DMS), diethyl sulphate (DES), benzyl chloride, benzyl bromine, and benzyl iodide. The reagents of benzyl bromine, and benzyl iodide were synthesized from benzyl chloride using NaBr in ethanol absolute and NaI in acetone, respectively. The five compounds of 5-nitro-1,10-phenanthroline hydrate 2 derivatives were conducted to evaluate the in vitro antiplasmodial activity. The in vitro antiplasmodial was evaluated on strains of Plasmodium falciparum FCR-3 resistant chloroquine and D10 sensitive chloroquine. The 50% inhibition concentration (IC50) of the five compounds ranged from 2.41±1.41 to 0.07±0.01 μM. The results showed that the (1)-N-benzyl-6-nitro-1,10-phenanthrolinium iodide had highest antiplasmodial activity.

New N-methylpiperazinyl derivatives of bicyclic antiprotozoal compounds

The 4-methylpiperazinyl group was inserted as substituent at the bridgehead of bicyclic compounds or as terminal group of their aminoacyl and aminoalkyl side chains. The new compounds were tested in vitro for their activities against the multidrug-resistant K 1 strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). The results were compared to those of formerly prepared analogues and of drugs in use. A couple of bicyclo-octyl ω-(4-piperazin-1-yl)alkanoates showed high antitrypanosomal (IC 50 ≤ 0.087 μM) and antiplasmodial activity (IC 50 ≤ 0.06 μM). The most active ω-(4-methylpiperazin-1-yl)alkyl-2-azabicyclo-nonane possessed higher antiplasmodial activity (IC 50 ≤ 0.023 μM) and selectivity (S.I. = IC 50 (Cytotox.)/IC 50 ( P. falciparum) = 2188) than the antimalarial drug chloroquine (IC 50 = 0.15 μM, S.I. = 1257).

Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections

Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of two new cucurbitane-type triterpenoids, balsaminol F (1) and balsaminoside B (2), along with the known glycosylated cucurbitacins, cucurbita-5,24-diene-3β,23(R)-diol-7-O-β-d-glucopyranoside (3) and kuguaglycoside A (4). Compound 1 was acylated yielding two new triesters, triacetylbalsaminol F (5) and tribenzoylbalsaminol F (6). The structures were elucidated based on spectroscopic methods including 2D-NMR experiments (COSY, HMQC, HMBC and NOESY). Compounds 1–6, were evaluated for their antimalarial activity against the erythrocytic stages of the Plasmodium falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2. Assessment of compounds (1–3 and 5, 6) activity against the liver stage of Plasmodium berghei was also performed, measuring the luminescence intensity in Huh-7 cells infected with a firefly luciferase-expressing P. berghei line, PbGFP-Luccon. Active compounds were shown to inhibit the parasite’s intracellular development rather than its ability to invade hepatic cells. Toxicity of compounds (1–3 and 5, 6) was assessed on the same cell line and on mouse primary hepatocytes through the fluorescence measurement of cell confluency. Furthermore, toxicity of compounds 1–6 towards human cells was also investigated in the MCF-7 breast cancer cell line, showing that they were not toxic or exhibited weak toxicity. In blood stages of P. falciparum, compounds 1–5 displayed antimalarial activity, revealing triacetylbalsaminol F (5) the highest antiplasmodial effects (IC50 values: 0.4μM, 3D7; 0.2μM, Dd2). The highest antiplasmodial activity against the liver stages of P.berghei was also displayed by compound 5, with high inhibitory activity and no toxicity.

&lt;i&gt;In vitro&lt;/i&gt; Antimalarial and Cytotoxic Activities of Leaf Extracts of &lt;i&gt;Vernonia amygdalina&lt;/i&gt; (Del.)

The antiplasmodial and cytotoxic activity of leaf extracts of Vernonia amygdalina was studied. The plant leaves were prepared into three extract forms: ethanolic, aqueous, and hydroethanolic (50:50) using standard procedures. The extracts were evaluated in vitro for antiplasmodial activity using a 3D7 chloroquine sensitive clone of NF-54 isolate of Plasmodium falciparum. The parasite growth inhibition was estimated based on the 48 hours microassay technique. Cytotoxicity of the extracts was evaluated in vitro using non-cancerous vero cell line (C-1008 kidney fibroblasts from African green monkey) by the neural red uptake method. The results showed that the ethanolic extract of the plant had the highest antiplasmodial activity with IC50 = 9.8 mg/ml, cytotoxicity (IC50 = 60.33) and selectivity index (S.I.) of 6.14 when compared with the other extracts. The results suggest that the ethanolic extract of V. amygdalina possesses considerable antiplasmodial activity. The study justifies local claims on the efficacy of the plant leaves for treatment of malaria.

Indole and aminoimidazole moieties appear as key structural units in antiplasmodial molecules

From a library of compounds of natural sources, a big series of molecules was chosen by random sampling to evaluate their in vitro antimalarial activity against Plasmodium falciparum and their antifungal activity against Candida sp. From 184 molecules tested, no molecules were active against Candida sp. (MIC > 10 μg/ml) whereas 13 clearly showed high antiplasmodial activity in vitro, with an IC 50 less than 1 μg/ml against the chloroquine-resistant strain of P. falciparum FcM29-Cameroon. The molecules with the best antiplasmodial efficacy were 10-hydroxy-ellipticin (IC 50: 0.08 μg/ml), tchibangensin (IC 50: 0.13 μg/ml), ellipticin hydrochloride (IC 50: 0.17 μg/ml), usambarensin (IC 50: 0.23 μg/ml), 7S,3S-ochropposinine oxindole (IC 50: 0.25 μg/ml), 3,14-dihydro-ellipticin (IC 50: 0.25 μg/ml), tetrahydro-4′,5′,6′17-usambarensin 17S (IC 50: 0.26 μg/ml), ellipticine (IC 50: 0.28 μg/ml), aricin (IC 50: 0.3 μg/ml), 10-methoxy-ellipticin (IC 50: 0.32 μg/ml), aplysinopsin (IC 50: 0.43 μg/ml), descarbomethoxydihydrogambirtannin (IC 50: 0.46 μg/ml) and ochrolifuanin A (IC 50: 0.47 μg/ml). Among these 13 promising molecules, all except descarbomethoxydihydrogambirtannin, ochrolifuanine A and usambarensine presented here novel biological activities since they had never been described in the literature for their antiplasmodial activity. In spite of the large diversity of the molecules which have been tested, it is interesting to note that the ones active against Plasmodium are all indole derivatives (and one is both indolic and aminoimidazolic). To find new antiplasmodial compounds, ethnopharmacological approaches studying traditional medicine treatments for malaria is largely used but random research produced here an interesting yield (7%) of new antiplasmodial hits and appears therefore complementary to the traditional medicine way.

Antiplasmodial and cytotoxicity activities of some selected plants used by the Maasai community, Kenya

Malaria has continued to be a major global public health problem and a health concern in most of African countries. An estimated 350–500 million cases of malaria each year result in about one million deaths, mainly children under five. The rate of malaria infection is increasing rapidly partly due to drug resistance by the Plasmodium falciparum. The cost of the current drugs is prohibitive to the poor. There is therefore urgent need to identify new antimalarial agents that are effective, safe and affordable. In our continuous search for these new antimalarial compounds, extracts from five medicinal plants from the Maasai community in Kenya were tested against P. falciparum (D6; chloroquine sensitive and W2; chloroquine resistant strains). Of the tested total plant extracts, 5 crude extracts showed good antiplasmodial activity against D6 strain of P. falciparum with IC 50 values lower or equal to 14.3 μg/ml, 2 were moderately active with IC 50 values in between 26.6 and < 50 μg/ml. The petroleum ether extracts of the aerial parts and roots of Fuerstia africana demonstrated high antiplasmodial activity against the chloroquine sensitive antiplasmodial strain D6 (IC 50 1.5 and 4.6 μg/ml, respectively with a selectivity index of 44 against vero cells). Manilkara discolor also exhibited promising antiplasmodial activity especially against D6 (IC 50 11.5 and 26.6 μg/ml). In addition, ethyl acetate extract of the roots of Pentas lanceolata and the aerial parts of Sericocomopsis hildebrandtii demonstrated moderate antiplasmodial activity against D6 and W2 (IC 50 14.3 and 16.51 μg/ml) respectively. F. africana therefore has high potential and can be pursued for the development of an antimalarial drug.

ChemInform Abstract: Recent Advances in the Stereochemical Determination and Total Synthesis of Myxobacterial Polyketides

AbstractReview: ca. 100 refs.

Estudo fitoquímico biomonitorado pelos ensaios de toxicidade frente à Artemia salina e de atividade antiplasmódica do caule de aninga (Montrichardia linifera)

Montrichardia linifera é uma planta aquática de amplo uso na medicina tradicional amazônica. Entretanto, muito pouco se conhece sobre a sua composição química, e sua atividade biológica ainda não foi comprovada. Na busca de substância(s) biologicamente ativa(s), este trabalho realizou um estudo fitoquímico biomonitorado no qual foram testados os extratos hexânico e etanólico obtidos do caule desta espécie, dos quais apenas o extrato etanólico foi selecionado para o fracionamento cromatográfico por ter apresentado toxicidade contra a Artemia salina e atividade contra o Plasmodium falciparum, parasita causador da malária. As atividades biológicas concentraram-se na fração diclorometânica que apresentou alta toxicidade contra A. salina (DL50&lt;31μg mL-1) e alta atividade antiplasmódica (IC50&lt;10 μg mL-1), mostrando promissora atividade antimalárica. Desta fração, o composto aromático p-hidroxibenzaldeído foi isolado pela primeira vez nesta planta.

In vitro antiplasmodial activity and cytotoxicity of nine plants traditionally used in Gabon

As part of a project to identify new compounds active on malarial parasites, we tested the in vitro antiplasmodial activity of nine plants traditionally used to treat malaria symptoms in Haut-Ogooué Province, South-East Gabon. Dichloromethane and methanolic extracts of each plant were tested for their antiplasmodial activity on two chloroquine-resistant strains of Plasmodium falciparum (FCB and W2), based on lactate dehydrogenase activity. Cytotoxicity was assessed with the MTT test on MRC-5 human diploid embryonic lung cells. The methanolic extract of Staudtia gabonensis and the dichloromethane extract of Adhatoda latibracteata showed high antiplasmodial activity (IC₅₀<1 μg/ml) and low cytotoxicity, with selectivity indexes of about 58.25 and 16.43, respectively. The methanolic extract of Monodora myristica and the dichloromethane extract of Afromomum giganteum also showed promising activity (1<IC₅₀<10 μg/ml) and low cytotoxicity, with selectivity indexes about 15.70 and 12.48, respectively. Dichloromethane extracts of Monodora myristica and Leonotis Africana showed moderate activity (10<IC₅₀<40 μg/ml), with selectivity indexes about 6.07 and 28.89, respectively. Both extracts of Culcasia lancifolia had IC₅₀ values of 10-40 μg/ml but high cytotoxicity (selectivity indexes <2.77). The methanolic extract of Dorstenia klaineana had moderate antiplasmodial activity (IC₅₀ around 17 μg/ml) but strong cytotoxicity (0.43 μg/ml), giving a selectivity index of about 0.03. Most extracts of nine selected plants traditionally used to treat malaria in Gabon had interesting antiplasmodial activity in vitro. This supports continued investigations of traditional medicines in the search for new antimalarial agents. The compounds responsible for the observed antiplasmodial effects are under investigation.

Recent Advances in the Stereochemical Determination and Total Synthesis of Myxobacterial Polyketides

Myxobacteria are a rich source of structurally diverse polyketides with unique architectures. Many of these compounds are associated with high biological activities, including antiproliferative, antibiotic, antifungal, and antiplasmodial activities, and in many cases specific targets are addressed at the molecular level. Unfortunately, many of these compounds were originally only reported as flat structures, impeding further advancement. In recent years, considerable progress has been made on the stereochemical determination and total syntheses of myxobacterial polyketides. This account highlights from a personal perspective illustrative examples of recent advances in the stereochemical determination and total synthesis of myxobacterial polyketides.

Antiplasmodial activity of botanical extracts against Plasmodium falciparum

The absence of a vaccine and the rampant resistance to almost all antimalarial drugs have accentuated the urgent need for new antimalarial drugs and drug targets for both prophylaxis and chemotherapy. The aim of the study was to discover effective plant extracts against Plasmodium falciparum. In the present study, the hexane, chloroform, ethyl acetate, acetone, and methanol extracts of Citrus sinensis (peel), Leucas aspera, Ocimum sanctum, Phyllanthus acidus (leaf), Terminalia chebula (seed) were tested for their antimalarial activity against chloroquine (CQ)-sensitive (3D7) strain of P. falciparum which was cultured following the candle-jar method. Antimalarial evaluations of daily replacement of culture medium containing CQ and different plant crude extracts were performed on 96-well plates at 37°C for 24 and 48 h. Parasitemia was determined microscopically on thin-film Giemsa-stained preparations. Plant extracts were tested for their cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on human laryngeal cancer cell line (HEp-2) and normal cell line (Vero). Out of the 25 extracts tested, six showed good (IC(50) 4.76-22.76 μg/mL), 15 exhibited moderate (IC(50) 31.42-88.03 μg/mL), while four displayed mild (IC(50) > 100 μg/mL) antiplasmodial activity. The leaf ethyl acetate and methanol extracts of L. aspera; ethyl acetate, acetone, and methanol extracts of P. acidus; and seed acetone extract of T. chebula had good antiplasmodial activity (IC(50) = 7.81, 22.76, 9.37, 14.65, 12.68, and 4.76 μg/mL) with selectivity indices 5.43, 2.04, 4.88, 3.35, 3.42, and 9.97 for HEp-2 and >5.79, >2.20, >11.75, >3.41, >3.94, and >7.38 for Vero cells, respectively. These analyses have revealed for the first time that the components present in the solvent extracts of L. aspera, P. acidus, and T. chebula have antiplasmodial activity. The high antiplasmodial activity observed make these plants good candidates for isolation of anti-protozoal compounds which could serve as new lead structures for drug development.

In vitro antiplasmodial activity of ethanolic extracts of mangrove plants from South East coast of India against chloroquine-sensitive Plasmodium falciparum.

Malaria is one of the most prevalent infectious diseases in the world. Treatment for malaria is commonly inadequate due to the lack of quality assured effective drugs. The effectiveness of these drugs is declining at an ever accelerating rate, with consequent increase in malaria related morbidity and mortality. The newest antiplasmodial drug from plants is needed to overcome this problem. Numerous mangroves and mangal associates are used as folklore medicine to treat various human diseases. The mangrove plant species are a good source of potential bioactive entities which exhibits many therapeutic properties. The present study was carried out to test the antiplasmodial activity of five mangrove plant species distributed along the South East coast of India. Bruguiera cylindrica, Ceriops decandra, Lumnitzera racemosa, Rhizophora apiculata, and Rhizophora mucronata mangrove plant extracts exhibited in vitro antiplasmodial activity against chloroquine-sensitive Plasmodium falciparum. Of which, the ethanolic bark extract of R. mucronata exhibited high antiplasmodial activity (IC(50)=62.18 μg.ml(-1)). Statistical analysis reveals that, significant antiplasmodial activity (P<0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out and it shows that no morphological differences in erythrocytes by the ethanolic extract of mangrove plants after 48 h of incubation. The screening for phytochemical constituents in the mangrove plants were carried out and it reveals that, the presence of alkaloids, triterpenes, flavonoids, tannins, catachin, anthroquinone, phenols, sugars, and proteins. This study shows that the mangrove plants had a source of lead compounds for the development of new drugs for the treatment of malaria.

2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections

Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway ( PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II ( PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC 50 value 6.6 μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC 50 value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescence analysis (IC 50 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC 50 values of 0.38 and 0.58 μg/ml (IC 50 control drugs 14 and 30 ng/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC 50 values 3.7–31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC 50 20.2 μg/ml), and Leishmania donovani (IC 50 values 4.1–13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to study the interaction of fatty acids with these key P. falciparum enzymes.

Phytochemical study of plants used in traditional medicine in the treatment of malaria in the Comoros islands

An ethnobotanical survey was carried out in the Comoros Islands about plant species used traditionally for the treatment of various diseases including malaria. The in vitro antiplasmodial activity of 76 vegetal extracts obtained from 17 species traditionaly used to treat malaria symptomes, was evaluated using Plasmodium falciparum choloroquine-resistant strain (W2). The results showed that 10 plant extracts had a moderate activity (5 &lt; IC50 ≤10µg/ml), and 6 showed particularly interesting in vitro activity with IC50 value ≤5µg/ml [1]. The phytochemical study realized on three selected plants, Flueggea virosa (Roxb. Ex Willd.) Voigt subsp. Virosa (Euphorbiaceae), Piper capense L.f. (Piperaceae), and Flacourtia indica (Burm. F.) Merr. (Flacourtiaceae) allowed us to isolate compounds from the most active extracts. The structures of isolated compounds were elucidated by spectrometric methods and their antiplasmodial activity was evaluated in vitro against the chloroquine-resistant strain W2 of Plasmodium falciparum, according to Azas, 2002 [2]. From F. virosa, rutine, gallic acid, methyl gallate, bergenin, (–)-norsecurinine, securinol A, N-methyltetrahydro-β-carboline and N-methyltryptamine were isolated. The highest antiplasmodial activity was found for methyl gallate (IC50=14.1µM). Together with apigenine dimethylether and piperchabamide A, a new amide alkaloid, Kaousine and the Z form of antiepilepsirine were isolated from the aerial part of P. capense. Lower activity was observed for kaousine and apigenine dimethylether, whereas antiepilepsirine demonstrated the same activity that the chloromethylenic extract of P. capense (IC50=7µg/ml) [3]. Pyrocatechol, homaloside D and poliothrysoside were isolated from the decoction of the aerial parts of F. indica. The poliothrysoside presented a strong antiplasmodial activity (IC50=7.4µM) and a good selectivity index (&gt;28) similar to chloroquine.

Antiplasmodial activity of sesquiterpene lactone from Carpesium rosulatum in mice

In the previous work, methanol extracts of Carpesium rosulatum (Compositae) were found to have high antiplasmodial activity against Plasmodium falciparum in vitro, this activity being largely attributable to a ineupatorolides A (I-A). In the present study, encouragingly, I-A was also found to have potential antimalarial activity in vivo when tested against Plasmodium berghei in mice. I-A (2, 5, 10 mg kg(-1) day(-1)) exhibited a significant blood schizontocidal activity in 4-day early infection, repository evaluation, and in established infection with a significant mean survival time comparable to that of the standard drug, chloroquine (5 mg kg(-1) day(-1)). The I-A possesses a promising antiplasmodial activity, which can be exploited in malaria therapy.

Atovaquone‐Statine “Double‐Drugs” with High Antiplasmodial Activity

Atovaquone‐Statine “Double‐Drugs” with High Antiplasmodial Activity

Potential antimalarial activity of indole alkaloids

New antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. Natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). Among the natural products, indole alkaloids represent an interesting class of compounds. Screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. This review covers the indole alkaloids with high antiplasmodial activity (in vitro and in vivo) isolated from natural sources, and is organized according to the different chemical structures of the alkaloids.

Antimalarial activity of crude extracts from nine African medicinal plants

An ethnobotanical study was conducted in Comores (Ngazidja) about plant species used traditionally for the treatment of various diseases, including malaria. Antimalarial activity of 76 vegetal extracts obtained from 17 species traditionally used to treat malaria symptoms, was evaluated in vitro using Plasmodium falciparum chloroquine-resistant strain (W2). Antiproliferative activity was evaluated on human monocytic THP1 cells and the selectivity index of the plant extracts was calculated. The results showed that 10 plant extracts had a moderate activity (5 < IC 50 ≤ 10 μg/ml), and 6 a good in vitro activity with IC 50 value ≤5 μg/ml. The highest antiplasmodial activity was found for the MeOH/H 2O leaves extract of Flueggea virosa (Roxb. Ex Willd.) Voigt subsp. virosa (Euphorbiaceae) (IC 50 = 2 μg/ml), for roots decoction of Flueggea virosa (IC 50 = 3 μg/ml) and for chloromethylenic roots extract of Vernonia colorata (Willd.) Drake subsp. grandis (DC.) C. Jeffrey (Asteraceae) (IC 50 = 3 μg/ml). Three other extracts showed moderate antiplasmodial activity (IC 50 < 5 μg/ml): Vernonia colorata (aerial part), Piper capense L.f. (Piperaceae), and Leptadenia madagascariensis Decne (Asclepiadaceae) chloromethylenic extracts (IC 50 = 6 μg/ml; 7 μg/ml and 9 μg/ml, respectively). All the plants tested displayed a low cytotoxicity on THP1 cells.