Antimalarial activity of Tiliacora triandra diels against Plasmodium falciparum in vitro

Preparations from the roots of the Thai medicinal plant, Tiliacora triandra Diels, were found to have antimalarial activity against Plasmodium fakiparum in vitro. Methanol extraction yielded two alkaloidal components (water-soluble and water-insoluble). Only the water-insoluble alkaloidal component showed an increase in antimalarial activity. From this component, five different alkaloids of the bisbenzyl-isoquinoline group were isolated and identified as tiliacorine, tiliacorinine, nor-tiliacorinine A, and two uncharacterized alkaloids G and H. Alkaloid G was found to be the most active in vitro schizontocide (ID₅₀, 344 ng/mL) followed by nor-tiliacorinine A and tiliacorine (ID₅₀, 558 and 675 ng/mL, respectively).     

Schizontocidal activity of Celastrus paniculatus Willd. against Plasmodium falciparum in vitro

Preparations from the plant Celastrus paniculatus Willd. have been used for treatment of malaria and other febrile illness in the traditional medicine practices of Thailand. Crude solvent extracts from the root bark and stem of C. paniculatus were screened for antimalarial activity against P. falciparum using an in vitro culture system. A fraction of the chloroform extract of the root bark showed the highest antimalarial activity. An active principle was isolated and characterized from the chloroform fraction and identified as a quinonoid triterpene, pristimerin. When tested in vitro against various multidrug resistant isolates of P. falciparum, pristimerin was less active than the conventional antimalarial drugs tested.     

Transformations of manool. tri- and tetracyclic norditerpenoids with in vitro activity against Plasmodium falciparum

The known 17-norisopimar-15-ene-8beta,13beta-diol (5) and five new semisynthetic norditerpenoids, ethyl 17-norabiet-13(15)-E-en-8beta-ol-16-oate (6), ethyl 17-norabiet-13(15)-Z-en-8beta-ol-16-oate (7), 17-norpimaran-13alpha-ethoxy-8,16-olactone (8), 17-norisopimarane-8beta,15-diol (9), and 17-norarabiet-13(15)-ene-8beta,16-diol (10), were prepared from manool (11). Standard spectroscopic data including X-ray crystal analysis were used to determine the structures of 5-10. All five compounds exhibited in vitro antiplasmodial activity against the malarial parasite Plasmodium falciparum at varying microg mL(-1) concentrations.     

Plants as sources of antimalarial drugs, Part 4: Activity of Brucea javanica fruits against chloroquine-resistant Plasmodium falciparum in vitro and against Plasmodium berghei in vivo

Extracts of Brucea javanica fruit have been prepared and monitored for their in vitro and in vivo antiplasmodial activities. The antimalarial activity of the fruit was found to be attributable to its quassinoid constituents. Nine of the quassinoids possessed in vitro IC50 values between 0.046-0.0008 microgram/ml against the chloroquine resistant Plasmodium falciparum strain (Kl) tested. The two quassinoid glycosides tested were considerably less active in vitro than the aglycones. Four quassinoids were found to possess activity in vivo against Plasmodium berghei infections in mice after oral dosing. All five quassinoids tested in vivo showed some toxicity.     

Furfuran lignans and a flavone from Artemisia gorgonum Webb and their in vitro activity against Plasmodium falciparum

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.     

Chemosensitizing action of cepharanthine against drug-resistant human malaria, Plasmodium falciparum

We have established a system of in vitro and in vivo assays to prioritize plant extracts that can serve as a source of drug candidates for the treatment of malaria, an infectious disease that affects nearly 40% of the world's population. In the present study, we have investigated the biological potential of one such plant-derived drug lead, cepharanthine. In vitro growth inhibition studies indicated this compound possessed good antiplasmodial activity without mediating a cytotoxic response. Based on this selectivity, evaluations were performed with an in vivo mouse model. Moderate activity was observed, inhibiting parasite growth by 46% at a dose of 100 mg/kg body weight (BW). We further assessed the ability of cepharanthine to serve as a drug in combination with a standard antimalarial regimen. Like chloroquine, cepharanthine inhibited the trophozoite stage of parasite growth. Isobolographic analyses revealed synergism with chloroquine, but only with the drug-resistant malaria clone, and single-dose drug-interaction studies demonstrated that cepharanthine lowered the half-maximal inhibitory concentration of chloroquine from 148.5 to 37.8 nM. In summary, since activity in the mouse model was only moderate, cepharanthine may be of greater value as a modulator of resistance, capable of prolonging the clinical utility of chloroquine.     

In vitro evaluation of the antiplasmodial activity of Dendropanax morbifera against chloroquine‐sensitive strains of Plasmodium falciparum

Dendropanax morbifera Leveille (Araliaceae) is well known in Korea traditional medicine for a variety of diseases. The methanol extract of the lower stem parts of D. morbifera was investigated for its activity against chloroquine‐sensitive strains of Plasmodium falciparum using the parasite lactate dehydrogenase assay method. Two cycloartane‐type glycosides oleifoliosides A (1) and B (2), and dendropanoxide (3), β‐amyrin (4), α‐amyrin (5) have been isolated from the stem parts of D. morbifera. All five compounds were evaluated for in vitro antiplasmodial activities as well as their cytotoxic potential on SK‐OV‐3 cancer cell lines. Compounds 2 and 3 showed notable growth inhibitory activity against chloroquine‐sensitive strains of Plasmodium falciparum with IC₅₀ values of 6.2 and 5.3 µm . This compound showed no significant cytotoxicity (IC₅₀ > 150 µm ) evaluated using SK‐OV‐3 cancer cell lines. This is the first report on the antiplasmodial activity of the compounds from D. morbifera. Copyright © 2009 John Wiley & Sons, Ltd.     

Activity of extracts and isolated naphthoquinones from Kigelia pinnata against Plasmodium falciparum

Four naphthoquinoids from Kigelia pinnata rootbark were assessed in vitro against chloroquine-sensitive (T9-96) and -resistant (K1) Plasmodium falciparum strains and for cytotoxicity using KB cells. 2-(1-Hydroxyethyl)naphtho[2,3-b]furan-4,9-dione possessed good activity against both strains [IC(50) values 627 nM (K1), 718 nM (T9-96)]. Isopinnatal, kigelinol, and isokigelinol exhibited lower activity against both strains.     

Potential antimalarial candidates from African plants: and in vitro approach using Plasmodium falciparum

Twenty-one compounds isolated from nine medicinal plants used in traditional medicine in the Sudan and other African countries were examined in vitro for antimalarial activity against Plasmodium falciparum, the major human malaria parasite. Compounds tested include alkaloids, lignans, triterpenes, coumarins, limonoids and flavonoids. Most were relatively inactive; one limonoid, gedunin, had an IC50 value of about 1 microM after 48 h exposure (0.3 microM after 96 h), roughly equivalent to quinine. In this protocol, the flavonoid quercetin purified from Diosma pilosa was found to have the same activity as a commercially obtained preparation. Simple radiometric assays for antimalarial activity can thus be used to rapidly screen purified plant material or secondary plant metabolites. The high potency and efficacy of quinine and the Chinese herbal antimalarial quinghaosu (artemisinine) illustrate the merit of this approach.     

Pseudoguaianolide sesquiterpene lactones with high activities against the human malaria parasite Plasmodium falciparum

Four sesquiterpene lactones of the pseudo-guaianolide type (helenalin, dihydrohelenalin and their acetates), have shown activities against asexual blood forms of Plasmodium falciparum in vitro. Their IC(50) values were situated in the range of 0.23 to 7.41 micro M. The activity found for helenalin was high, even compared to the activity found for artemisinin.     

Antiparasitic compounds from Cupania cinerea with activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense

In a survey of plants from Ecuador with antiprotozoal activity, Cupania cinerea was found to show significant in vitro activity against the Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense. Subsequently, activity-guided isolation of the n-hexane and dichloromethane extracts from the bark of C. cinerea afforded two diterpene glycosides (1 and 2), named cupacinoside and 6'-de-O-acetylcupacinoside, and a lactonized triterpene bearing an oxepin moiety named cupacinoxepin (3), together with the known compounds scopoletin (4), caryophyllene oxide (5), two bisabolane sesquiterpenes (6 and 7), lichexanthone (8), gustastatin (9), lupenone (10), betulone (11), 17β,21β-epoxyhopan-3-one (12), taraxerol (13), and taraxerone (14). For compound 3, X-ray crystallography was employed to elucidate the relative configuration. For cupacinosides (1) and (2) and cupacinoxepin (3), in vitro activities against the P. falciparum K1 strain (IC(50)1, 1.3; 2, 1.8; and 3, 8.7 μM) and T. b. rhodesiense (IC(50)1, 4.5; 2, 15.8; and 3, 71.6 μM) were found. Cytotoxicity toward L-6 cells is discussed for all the compounds isolated.     

Antiprotozoal activity of drimane and coloratane sesquiterpenes towards Trypanosoma brucei rhodesiense and Plasmodium falciparum in vitro

The extracts and 12 sesquiterpenes obtained from the East African medicinal plant Warburgia ugandensis Sprague (Canellaceae) were assessed for their antiplasmodial activity against the chloroquine‐sensitive (3D7) and chloroquine‐resistant (K1) strains of Plasmodium falciparum and antitrypanosomal activity against Trypanosoma brucei rhodesiense. The dichloromethane extract displayed strong antiplasmodial and antitrypanosomal activities with IC₅₀ values of 8.10 and 1.10 µg/mL against K1 strain of the malaria parasite and STlB900 strain of T. b. rhodesiense, respectively. Among the compounds evaluated for inhibition of trypomastigotes, both drimane and coloratane sesquiterpenes possessing aldehyde groups at positions 8 and 9 were found to show most antitrypanosomal activity with IC₅₀ values in the range 0.56–6.4 µM. The antiplasmodial assays also revealed that the six coloratane and six drimane sesquiterpenes isolated from this extract exhibited significant antitrypanosomal activity with IC₅₀ values ranged from 0.45 to ?114 µM. Among the compounds tested against the malarial parasite P. falciparum 11?‐hydroxymuzigadiolide (3) was most active with an IC₅₀ value of 6.40 µM. Copyright © 2010 John Wiley & Sons, Ltd.     

Cytotoxic and antitumour activity of scopadulcic acid from Scoparia dulcis L.

Scopadulcic acid B is a diterpenoid recently isolated from Scoparia dulcis L. This compound showed greater cytotoxicity against cell lines derived from tumour tissues with a 50% inhibitory concentration (IC₅₀) of 0.068–0.076 μg/mL, compared with cell lines from normal tissues with an IC₅₀ of 0.097–0.245 μg/mL. The in vivo antitumour activity of scopadulcic acid B was determined using mice inoculated with Ehrlich ascites tumour cells. Oral administration of the compound at doses of 25 or 100 mg/kg/day prolonged the median survival time of the animals. However, when administered intraperitoneally to mice at doses of 25, 50 or 100 mg/kg/day, scopadulcic acid B increased the survival rate by 12.5%, 12.5% and 25%, respectively, without weight change over the treatment period.     

Antiparasitic compounds from Cornus florida L. with activities against Plasmodium falciparum and Leishmania tarentolae

Aim of the study

The objective of this study was to identify the antiplasmodial constituents from the bark of Cornus florida L., a plant traditionally used in North America for the treatment of malaria.

Methods and materials

Dried and powdered bark was extracted with 95% ethanol. The resultant extract was subjected to in vitro antiplasmodial-guided fractionation against Plasmodium falciparum (D10 strain). Antiplasmodial IC₅₀ values were calculated for pure compounds. Compounds were also assayed against Leishmania tarentolae, and rat skeletal myoblast L6 cells to assess antileishmanial activity and cytotoxicity, respectively.

Results

Antiplasmodial-guided fractionation afforded 8 compounds: betulinic acid (1), ursolic acid (2), β-sitosterol (3), ergosta-4,6,8,22-tetraene-3-one (4), 3β-O-acetyl betulinic acid (5), 3-epideoxyflindissol (6), 3β-O-cis-coumaroyl betulinic acid (7), 3β-O-trans-coumaroyl betulinic acid (8), of which, (6) is for the first time here isolated from a natural product and (4), (7) and (8) are reported for the first time from this genus. In vitro IC₅₀ values against P. falciparum for (4) (61.0 μM) (6) (128.0 μM), (7) (10.4 μM), (8) (15.3 μM) are reported for the first time. Antileishmanial IC₅₀ values are reported here for the first time for (4) (11.5 μM), (6) (1.8 μM), (7) (8.3 μM) and (8) (2.2 μM). Cytotoxicity against L6 cells is reported for all compounds.

Conclusions

The compounds isolated in this study, while displaying moderate in vitro antiplasmodial activity, do not fully support the historical importance of C. florida as an antimalarial remedy in North America. The traditional remedy may exert its well documented effects by mechanisms unrelated to direct antiplasmodial action. While not traditionally used to treat Leishmania, this work shows that several constituents of C. florida possess promising in vitro antileishmanial activity.     

Antimalarial activity of natural product extracts from Papua New Guinean and Australian plants against Plasmodium falciparum

In the search for new antimalarial compounds, a subset of a natural product extract library prepared from plant samples collected from Papua New Guinea and Australia was screened for in vitro activity against the chloroquine-sensitive 3D7 and chloroquine-resistant Dd2 strains of Plasmodium falciparum. Using the incorporation of ((3)H)-hypoxanthine into parasite nucleic acid as a marker of growth, 93 of the 794 extracts screened displayed >40% inhibition against 3D7 infected erythrocytes at 312 microge/mL. Antimalarial activity was confirmed in 48 of these extracts against both 3D7 and Dd2 infected erythrocytes at concentrations between 78 and 390 microge/mL, 14 of which caused >90% growth inhibition of 3D7 at the lowest concentration screened. Extracts were also tested for mammalian cell cytotoxicity to evaluate selectivity of action.     

In vitro interactions of Aspilia africana (Pers.) C.D. Adams, a traditional antimalarial medicinal plant, with artemisinin against Plasmodium falciparum

Traditional antimalarial medicinal preparations are widely used concurrently with antimalarial drugs in malaria endemic areas. The plant Aspilia africana (Pers.) C.D. Adams is commonly used for traditional treatment of malaria symptoms in East and Central Africa. An in vitro study of interactions between an extract from this plant with artemisinin against two strains of Plasmodium falciparum showed an antagonist relationship against both the chloroquine-sensitive D10 and the chloroquine- and sulphonamide-resistant K1 strains of Plasmodium falciparum. The extract reduced accumulation of radiolabelled dihydroartemisinin ((3)H-DHA) by erythrocytes infected with the chloroquine- and sulphonamide-resistant K1 strain of Plasmodium falciparum while it increased its accumulation by erythrocytes infected with the chloroquine-sensitive D10 strain. These results suggest complex interactions between the antimalarial medicinal plant and artemisinin. This study also proposes an in vitro approach to investigating interactions between antimalarial drugs and traditional medicines.     

Cassane- and norcassane-type diterpenes from Caesalpinia crista of Indonesia and their antimalarial activity against the growth of Plasmodium falciparum

The CH2Cl2 extract of the seed kernels of Caesalpinia crista, which exhibited promising antimalarial activity against Plasmodium berghei-infected mice in vivo, was examined and resulted in the isolation of seven new furanocassane-type diterpenes [caesalpinins C-G (1-5) and norcaesalpinins D and E (6, 7)] together with norcaesalpinins A-C (8-10) and 11 known compounds (norcaesalpinins A-C, 2-acetoxy-3-deacetoxycaesaldekarin e, caesalmin B, caesaldekarin e, caesalpin F, 14(17)-dehydrocaesalpin F, 2-acetoxycaesaldekarin e, 7-acetoxybonducellpin C, and caesalmin G). Their structures were determined on the basis of spectroscopic analysis. The isolated diterpenes showed significant dose-dependent inhibitory effects on Plasmodium falciparum FCR-3/A2 growth in vitro. Their IC50 values ranged from 90 nM to 6.5 microM, and norcaesalpinin E (7) showed the most potent inhibitory activity (IC50, 90 nM).     

Efficacy of some nupe medicinal plants against Salmonella typhi: an in vitro study

Different medicinal plants: Euphobia hirta (Eh); Citrus aurantifolia (Ca), Cassia occidentalis (Co), and Cassia eucalyptus (Ce), which are claimed by the Nupes of Bida in Niger State of Nigeria to be effective in the treatment of typhoid fever were collected. Ethanolic and water extracts were obtained by standard procedures. Preliminary phytochemical screening showed that alkaloids were absent in all the parts of Eh, Co, and Ca studied, but present in all the parts of Ce studied. Saponins were absent in the leaves and florescence of Eh, Ca fruits, but present in little amounts in Eh and Co roots. Saponins were present in large amounts in all the parts of Ce studied. Tannins were in little amount in all the medicinal plants studied, except in Ca. Glycosides were not present in any of the medicinal plants studied. The in vitro and microbial analysis showed that only Ce showed inhibition to Salmonella typhi growth. Ca plus 'Kanwa' (a locally mined, alkaline salt) showed inhibition only at a high concentration of 'Kanwa'. The MIC and MBC of Ce are 1 and 2 mg/ml, respectively. The paper concludes that, of all the medicinal plants claimed by the Nupes to be effective against S. typhi, only Ce contains the natural compound that can be used in the treatment of typhoid fever.     

没食子酸抑制白念珠菌生物膜作用的研究

目的:研究没食子酸对体外白念珠菌生物膜的影响.方法:采用XTT减低法评价没食子酸对白念珠菌的生物膜及黏附性的影响;镜下观察没食子酸对白念珠菌生物膜的形态学影响;细胞毒试验检测该药的毒副作用.结果:没食子酸抑制白念珠菌生物膜最低药物浓度SMIC_(50),SMIC_(80)分别是500,1 000 mg·L~(-1);100,1 000 mg·L~(-1) 的没食子酸对白念珠菌的早期黏附及菌丝生长有抑制作用;没食子酸对人细胞毒性较弱.结论:没食子酸对体外白念珠菌生物膜有较强的抑制作用.     

Antiplasmodial studies of Eurycoma longifolia Jack using the lactate dehydrogenase assay of Plasmodium falciparum

The roots of Eurycoma longifolia Jack have been used as traditional medicine to treat malaria. A systematic bioactivity-guided fractionation of this plant was conducted involving the determination of the effect of its various extracts and their chemical constituents on the lactate dehydrogenase activity of in vitro chloroquine-resistant Gombak A isolate and chloroquine-sensitive D10 strain of Plasmodium falciparum parasites. Their antiplasmodial activity was also compared with their known in vitro cytotoxicity against KB cells. Four quassinoids, eurycomanone (1), 13,21-dihydroeurycomanone (3), 13 alpha(21)-epoxyeurycomanone (4), eurycomalactone (6) and an alkaloid, 9-methoxycanthin-6-one (7), displayed higher antiplasmodial activity against Gombak A isolate but were less active against the D10 strain when compared with chloroquine. Amongst the compounds tested, 1 and 3 showed higher selectivity indices obtained for the cytotoxicity to antiplasmodial activity ratio than 14,15 beta-dihydroxyklaineanone (2), eurycomanol (5), 6 and 7.