Antimalarial activity of Tanzanian medicinal plants

Tanzanian medicinal plants were extracted and tested for in vitro antimalarial activity, using the multidrug resistant K1 strain of Plasmodium falciparum. Of 49 plants investigated, extracts of three plants were found to have an IC50 between 5-10 micrograms/ml, extracts of 18 other plants showed an IC50 between 10 and 50 micrograms/ml, all others were less active. The three most active extracts were obtained from the tubers of Cyperus rotundus L. (Cyperaceae), the rootbark of Hoslundia opposita Vahl. (Labiatae), and the rootbark of Lantana camara L. (Verbenaceae).     

In vitro antimalarial activity and cytotoxicity of cochlospermum tinctorium and C. planchonii leaf extracts and essential oils.

The antimalarial and toxicological properties of Cochlospermum tinctorium and C. planchonii extracts and essential oils prepared from their leaves were studied. The oil components were extracted by hydrodistillation of the plant leaves and characterized by gas chromatography and mass spectrometry. Crude extracts and oils were tested for in vitro antimalarial activity on Plasmodium falciparum. The IC50 were evaluated after 24 and 72 h contact between the oils and the parasite culture, and ranged from 22 to 500 micrograms/ml. C. planchonii leaf oil yielded the best antimalarial effect (IC50: 22-35 micrograms/ml), while the most potent effect from crude leaf extracts was induced by C. tinctorium. The cytotoxicity of the leaf crude extracts and oils was assessed on the K562 cell line and showed IC50 values ranging between 33 and 2000 micrograms/ml.     

Antimalarial activity of Tanzanian plants and their active constituents: the genus Uvaria.

Petroleum ether, dichloromethane, and methanol extracts of leaves, stem, and root bark of nine Uvaria species: U. dependens, U. faulknerae, U. kirkii, U. leptocladon, U. lucida ssp. lucida, Uvaria sp. (Pande)k U scheffleri, and U. tanzaniae were tested for their in vitro activity against the multidrug resistant K1 strain of Plasmodium falciparum. The IC50 values of the extracts varied between 5 and 500 micrograms/ml. The most active extracts were obtained from the stem and root bark of U. lucida ssp. lucida and Uvaria sp. (Pande) and the root bark of U. scheffleri, all of which had IC50 values between 5 and 9 micrograms/ml. Among the compounds isolated, uvaretin, diuvaretin, and (8',9'-dihydroxy)-3-farnesylindole were the most active (IC50 = 3.49, 4.20, and 2.86 micrograms/ml, respectively).     

In Vitro Antimalarial Activity of Brucea javanica against Multi-Drug Resistant Plasmodium falciparum.

The medicinal plant, BRUCEA JAVANICA (L.) Merr. (Simaroubaceae) was examined for antimalarial properties. Among different crude solvent extracts of the fruit, the chloroform extract was shown to have the most potent IN VITRO antimalarial activity. Three active compounds were isolated and purified from the chloroform extract. These compounds were confirmed as bruceine A, bruceine B hydrate and bruceine C by UV, IR, NMR and mass spectra. When tested IN VITRO against multi-drug resistant isolates of P. FALCIPARUM bruceine A and bruceine B hydrate were similar in activity (ID50 of 8.66 and 8.15 ng/ml) whereas bruceine C had an ID50 of 1.95 ng/ml. These compounds were comparable in IN VITRO activity to the new antimalarial drug, mefloquine (ID50 of 6.26 ng/ml).     

Studies on the antiplasmodial properties of some South African medicinal plants used as antimalarial remedies in Zulu folk medicine

The parasite lactate dehydrogenase (pLDH) assay method, a recently developed in vitro enzymatic method for evaluating antimalarial compounds, was used to examine the antiplasmodial activities of the aqueous leaf, stem-bark and fruit extracts of some plants used for the treatment and/or prophylaxis of malaria in KwaZulu-Natal province of South Africa. The in vitro antiplasmodial assay was carried out using a chloroquine-sensitive strain of malarial parasite, Plasmodium falciparum D10. A preliminary phytochemical analysis of the plant extracts was carried out using UV spectral analysis and thin-layer chromatography (TLC) to separate the chemical constituents of the extracts. Their chemical components were subsequently identified by treating the TLC plates with various spray reagents. Of the 14 plant extracts investigated, only 10 were found to have IC50 values of 10-50 micrograms/ml. The two most active extracts were Psidium guajava stem-bark extract and Vangueria infausta leaf extract, both of which showed IC50 values of 10-20 micrograms/ml. Phytochemical analysis of these two active plant extracts revealed the presence of anthraquinones, flavonoids, seccoirridoids and terpenoids.     

New lanostanoids from Ganoderma lucidum that induce NAD(P)H:quinone oxidoreductase in cultured hepalcic7 murine hepatoma cells

Two new lanostanoids were isolated from the basidiocarp of Ganoderma lucidum and were identified as 26,27-dihydroxy-5 alpha-lanosta-7,9(11),24-triene-3,22-dione (1) and 26-hydroxy-5 alpha-lanosta-7,9(11),24-triene-3,22-dione (2) by their respective spectral data. Crude extracts and the isolated compounds were tested for their potential to induce NAD(P)H:quinone oxidoreductase (QR), a phase 2 drug-metabolizing enzyme, as an approach to detect potential cancer chemopreventive activity. Compound 2 doubled the specific activity of QR at a concentration of 3.0 micrograms/ml, whereas compound 1 was significantly less active (1.7-fold induction at 20 micrograms/ml). In addition, both compounds weakly inhibited sheep vesicle cyclooxygenase 1 activity at a test concentration of 40 micrograms/ml.     

Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots

The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5/5a) and quindoline (6), were isolated from the ethanolic and chlorophormic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and seven alkaloids isolated from those extracts were tested in vitro against Plasmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-sensitive clone). All the extracts were shown to give 90% inhibition of P. falciparum K1 growth at concentrations < 23 micrograms/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 microM to K1; 0.059 microM to T996) comparable with chloroquine (0.26 microM to K1; 0.019 microM to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most active with IC50 values of 0.8 microM (K1) and 1.2 microM (T996). Cryptolepinoic acid (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 microM). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenzazepine alkaloid 7. It was noticed that alkaloids with weakly basic characteristics were active whereas other structurally related alkaloids with different acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines.     

Antiplasmodial and cytotoxic activity of galipinine and other tetrahydroquinolines from Galipea officinalis

The antimalarial and toxicological properties of four tetrahydroquinoline alkaloids from Galipea officinalis trunk bark were studied. Crude extracts and pure alkaloids were tested for in vitro antimalarial activity on Plasmodium falciparum. The IC50 were evaluated after 24 and 72 h contact between compounds and the parasite culture, and ranged from 1.8 to 40 microg/ml for the chloroquine-sensitive strain (CQS) and from 0.09 to 38 microg/ml for the chloroquine-resistant strains (CQR). Galipinine yielded the best antimalarial effect (IC50: 0.09 - 0.9 microg/ml on CQR strain) and this compound interacted particularly between the 32(nd) and the 40(th) hour of the P. falciparum erythrocytic cycle. The cytotoxicity of the extracts and pure tetrahydroquinoline alkaloids was assessed on the HeLa cell line and showed IC50 values ranging from 5.8 to above 50 microg/ml.     

Antimalarial Activity of Some Kenyan Medicinal Plants

This paper describes the in vitro antimalarial activity of eight species of plants popularly used traditionally to treat malaria in Kenya. Organic and aqueous extracts from different parts of the plants were tested. Generally, a stronger antimalarial activity was observed in the organic extracts. The most active extracts were of Vernonia brachycalyx O. Hoffm. Schreber. (Compositae) leaves which showed an IC 50 of 6.6 µg/ml for methylene chloride: ethyl acetate (1:1) extracts, while the aqueous and more polar methanolic extracts gave IC 50 values of 29.6 and 30 µg/ml, respectively. The findings of this study support the use of this plant as a traditional remedy for malaria. The rest of the plants tested gave IC 50 values between 30–100 µg/ml.     

Optimization and comparison of three methods for extraction of volatile compounds from Cyperus rotundus evaluated by gas chromatography-mass spectrometry

The essential oil of Cyperus rotundus has multiple pharmacological activities. Therefore, the extraction with high yield and quality is very important for preparation of essential oil of C. rotundus. In this paper, three methods, namely hydrodistillation (HD), pressurized liquid extraction (PLE) and supercritical fluid extraction (SFE), for extraction of volatile compounds from C. rotundus were optimized and compared by gas chromatography-mass spectrometry. Among eight identified compounds in C. rotundus, five components including alpha-copaene, cyperene, beta-selinene, beta-cyperone and alpha-cyperone were quantitatively determined or estimated using alpha-cyperone as standard, which showed that PLE had the highest extraction efficiency, while SFE had the best selectivity for extraction of beta-cyperone and alpha-cyperone. The contents of ingredients from C. rotundus extracted with HD, PLE and SFE are significantly different, which suggest that comparison of chemical components and pharmacological activities of different extracts is helpful to elucidate the active components in C. rotundus and control its quality.     

Antimicrobial activity of clavines

The antimicrobial activity of two clavine-type ergot alkaloids (agroclavine, festuclavine), and 16 derivatives against four human pathogenic bacteria and Candida albicans was determined. It is shown that all ergolines tested with one exception exhibit antibacterial properties against one to four bacteria species. The most active compounds are 6-allyl-6-norfestuclavine (minimal inhibitory concentration (MIC) 30 micrograms/ml against Staphylococcus aureus), 1-propyl-6-norfestuclavine (MIC 60 micrograms/ml against Escherichia coli), 6-cyano-6-norfestuclavine (MIC 250 micrograms/ml against Pseudomonas aeruginosa), and 1-methyl-agroclavine (MIC 200 micrograms/ml against Proteus vulgaris). 1-Allyl-6-norfestuclavine and 1-propyl-6-norfestuclavine showed a broad action spectrum: the growth of all four bacteria species and of Candida albicans was inhibited. The most effective antifungal compounds are 1-propyl-6-norfestuclavine and 6-cyano-6-norfestuclavine (MIC 250 micrograms/ml). Three alkaloids of different structure (codeine, emetine, quinine) are inactive up to 500 micrograms/ml against the bacteria species and C. albicans. The acute toxicity (mouse) is remarkably diminished by the modifications of the natural clavines.     

Antifungal actinomycete metabolites discovered in a differential cell-based screening using a recombinant TOPO1 deletion mutant strain.

In the course of a natural product screening for inhibitors of fungal topoisomerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS 1465 exhibited promising activities. Bioguided fractionation of the culture broth by preparative HPLC methods yielded the collismycins A (1) and B (2) as active principles of strain WS 1410. Out of the mycelial extracts of strain BS 1465 the bioactive new natural products, cyclo-homononactic acid (3) and cyclo-nonactic acid (5) and the structurally related but inactive homononactic acid (4), were isolated. Both collismycin isomers inhibited the recombinant yeast strains ScAL 141 and ScAL 143 (TOPO 1 deletion mutant) in a non-specific manner with an MIC in the range of 2 micrograms/ml. The novel cyclo-homononactic acid (3) and cyclo-nonactic acid (5) showed higher selectivity towards the wild type strain (MIC = 2 micrograms/ml as compared to 10 micrograms/ml for the deletion mutant). All compounds obviously address a target other than TOPO 1 since they do not exhibit activities in a concurrent TOPO 1 enzyme assay.     

Biologically active steroidal glycosides from Tribulus terrestris

The steroidal saponin constituents obtained from Tribulus terrestris were tested for their antimicrobial and cytotoxic effects. The spirostanol-based steroidal saponins 1-3 exhibited remarkable activity against fungal organisms (Candida albicans and Cryptococcus neoformans) and cancer cell lines [human malignant melanoma (SK-MEL), human oral epidermoid carcinoma (KB), human breast ductal carcinoma (BT-549), and human ovary carcinoma (SK-OV-3)], while none of the compounds possessing the furostanol framework 4-7 showed activity. The most active spirostanol glycoside, compound 3 exhibited a broad range of anticancer activity against cell lines, SK-MEL, KB, BT-549 and SK-OV-3 at IC50s of 6.0, 7.0, 6.0 and 8.2 micrograms/ml, respectively, while compounds 1 and 2 showed selective cytotoxicity against SK-MEL at 6.7 and 9.1 micrograms/ml, respectively. The minimum inhibitory concentrations (MIC) in antifungal bioassay for compounds 1-3 varied from 1.5 to 6.2 micrograms/ml, which prompted to conclude certain structural features are required for these bioactivities.     

In vitro and in vivo characterization of novel 8-methoxy derivatives of chlortetracycline

The in vitro activities of three new 8-methoxychlortetracyclines, Sch 36969, 33256 and 34164 were compared to tetracycline, minocycline and doxycycline. Against aerobic Gram-negative rods Sch 36969 had a geometric mean MIC (GMM) of 4.2 micrograms/ml, about 8-fold more potent than Sch 33256, and similar to all the other compounds. Sch 36969 also had good activity against methicillin-resistant (GMM, 0.21 micrograms/ml) and -susceptible Staphylococci (GMM, 0.14 micrograms/ml), Streptococci (GMM, 0.06 micrograms/ml), and most anaerobic bacteria (GMM, less than 0.5 micrograms/ml). In general, Sch 36969 was similar to, or more potent than, all the other compounds tested. Serum levels of Sch 36969 in squirrel monkeys were 4-fold lower (AUC, 4.5 micrograms.hours/ml) than those of chlortetracycline (AUC, 16.1 micrograms.hours/ml). In mouse protection tests (PD50s) against various strains of bacteria, Sch 36969 was similar in activity to tetracycline, but up to 6-fold less active than chlortetracycline. The structure activity relationships for these new chlortetracyclines are described.     

Antimalarial activity of herbal extracts used in traditional medicine in Korea

Aqueous extracts of 6 traditional Korean medicines used to treat malaria were tested in vitro for their antimalarial activity against Plasmodium falciparum. The EC50 values for the herbal extracts were in the range 1.4-8.1 microg/ml. Significant antimalarial activity was observed with Coptis japonica (EC50=1.4 microg/ml), but it demonstrated no selective toxicity (selectivity=1). In contrast, Kalopanax pictus showed antimalarial activity (EC50=4.6 microg/ml) and higher selective toxicity (>4). This indicated that K. pictus may be potent for a new antimalarial agent.     

Interaction of various Piper methysticum cultivars with CNS receptors in vitro.

Methanolic leaf and root extracts of the Hawaiian kava (Piper methysticum Forst.) cultivars, Mahakea, Nene, Purple Moi and PNG, were tested on binding affinities to CNS receptors including GABAA (GABA and benzodiazepine binding site), dopamine D2, opioid (mu and delta), serotonin (5-HT6 and 5-HT7) and histamine (H1 and H2). HPLC analysis was carried out in order to determine the amount of the main kavalactones kavain, 7,8-dihydrokavain, methysticin, 7,8-dihydromethysticin, yangonin and 5,6-demethoxyyangonin. The most potent binding inhibition was observed for leaf extracts to GABAA receptors (GABA binding site) with IC50 values of approximately 3 micrograms/ml, whereas root extracts were less active with IC50 values ranging from 5 micrograms/ml (Nene) to 87 micrograms/ml (Mahakea). Since the leaf extracts generally contained lower amounts of the kavalactones than the root extracts, there might exist additional substances responsible for these activities. Leaf extracts also inhibited binding to dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors more potently than the corresponding root extracts with IC50 values ranging from 1 to 100 micrograms/ml vs. > or = 100 micrograms/l, respectively. Significant differences in the potential of binding inhibition were also observed between cultivars. Binding to serotonin (5-HT6 and 5-HT7) and benzodiazepine receptors was only weakly inhibited by both root and leaf extracts of all four cultivars. In conclusion, our investigation indicates that the GABAA, dopamine D2, opioid (mu and delta) and histamine (H1 and H2) receptors might be involved in the pharmacological action of kava extracts. Since the cultivars contained similar amounts of kavalactones, while their pharmacological activities differed markedly, other constituents may play a role in the observed activities. Additionally, leaves generally exhibited more potent binding inhibition than roots, therefore leaf of P. methysticum might be an interesting subject for further pharmacological studies.     

Assessment of antimycobacterial activity of a series of mainly marine derived natural products

A series of mainly marine derived natural products were tested for their activities against Mycobacterium tuberculosis and M. avium. Of the thirty-nine compounds tested fifteen demonstrated minimum inhibition concentrations (MICs) of 32 micrograms/ml or less, and eleven had MICs of 16 micrograms/ml or less. The most active compound found in this study was the sponge derived metabolite axisonitrile-3 (MIC 2 micrograms/ml).     

The comparative activity of twelve 4-quinolone antimicrobials against gram-positive and gram-negative anaerobes

The minimal inhibitory concentrations (MICs) of twelve 4-quinolone antimicrobials were determined for the Bacteroides fragilis group (50), Bacteroides melaninogenicus (20), Bacteroides bivius (10), Fusobacterium spp. (10), anaerobic Gram-positive cocci (50) and Clostridium spp. (20). MICs were determined using an agar dilution technique in Mueller-Hinton agar supplemented with 10% lysed horse blood. The inoculum used was approximately 10(4) colony-forming units, contained in 10 microliter of Mueller-Hinton broth, which was applied to the agar plates using a multipoint inoculator. Following inoculation, plates were incubated at 37 degrees C for 48 h in an anaerobic atmosphere. The MIC of each antimicrobial for each isolate examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the organism examined were also determined. All of the more recently synthesised 4-quinolones showed increased activity against the anaerobic bacteria used in this study. Ciprofloxacin and ofloxacin were the most active compounds examined (Bacteroides fragilis group MIC90 ciprofloxacin 4 micrograms/ml; ofloxacin 4 microgram/ml; Bacteroides melaninogenicus MIC90 ciprofloxacin 2 micrograms/ml, ofloxacin 2 micrograms/ml; Bacteroides bivius MIC90 ciprofloxacin 16 micrograms/ml, ofloxacin 32 micrograms/ml; Fusobacterium spp. MIC90 ciprofloxacin 2 micrograms/ml, ofloxacin 4 micrograms/ml; Clostridium spp. MIC90 ciprofloxacin 1 microgram/ml, ofloxacin 1 microgram/ml and anaerobic Gram-positive cocci MIC90 ciprofloxacin 4 micrograms/ml, ofloxacin 4 micrograms/ml).     

Synthesis and antimicrobial activities of some new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives of amoxicillin

A number of 6-[2-(dihydro-5-substituted-6-thioxo-2H-1,3,5-thiadiazine-3( 4H)-yl)-2-(4-hydroxyphenyl)acetamido]penicillanic acids has been synthesized as prodrugs by incorporating the amine group of amoxicillin trihydrate into tetrahydro-2H-1,3,5-thiadiazine-2-thione ring. The compounds have been prepared by the reaction of various alkyl or aralkyl amines with potassium hydroxide, carbon disulfide, formaldehyde and amoxicillin trihydrate. The structures of the compounds have been elucidated by UV, IR, 1H-NMR spectra and elementary analysis. The in vitro activity of these compounds against gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea, C. pseudotropicalis) was investigated by the tube dilution method and compared with the activity of amoxicillin trihydrate. By this way their minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) values were determined. Compound I and Compound VII were significantly more effective than amoxicillin trihydrate against S. aureus (MBC: 6.25 micrograms/ml). Compound VI and Compound XI were effective against S. faecalis (MBC: 6.25 micrograms/ml) and Compound I and Compound VI were effective against E. coli (MBC: 12.5 micrograms/ml). All of the compounds and amoxicillin trihydrate were ineffective against P. aeruginosa (MIC: greater than 100 micrograms/ml). Compound IX and Compound X were the most active derivatives against yeast-like fungi; the MFC values for these compounds ranged between 6.25 and 37.5 micrograms/ml.     

Antimalarial Activity of Khaya Grandifoliola Stem-bark

Khaya grandifoliola (Welw) CDC (Meliaceae) is widely used in West Africa for the treatment of fever. The dried powdered stem-bark of the plant was extracted with various solvents. The resulting extracts and column purified fractions therefrom were tested for their antimalarial properties using Plasmodium berghei berghei for in vivo antimalarial determinations and Plasmodium falciparum for in vitro antiplasmodial activities. The n -hexane extract, the crude and purified fractions gave the most active antimalarial activities with about 91% chemosuppression in vivo and IC 50 values of 1.4 µg/ml (for multi-drug resistant clone) or 0.84 µg/ml (for Nigerian P. falciparum isolates). These values were comparable to those observed with the reference drug chloroquine diphosphate.