Antimalarial activity of fractions isolated from Albizia gummifera and Aspilia mossambicensis crude extracts

To identify the fractions of medicinal plant extracts containing the highest concentration of antimalarial principles, we tested the antimalarial activities of the crude or total extracts and two fractions from Albizia gummifera (Leguminosae) and three fractions from Aspilia mossambicencis (Compositae) against laboratory adapted isolates of Plasmodium falciparum in vitro using the 3H-hypoxanthine uptake assay. Chloroquine was used as a reference antimalarial drug. The mean 50% inhibitory concentrations (IC50s) of A. gummifera total extract and fraction were both <2.2 microg/ml for three P. falciparum isolates while the mean IC50 of A. gummifera f raction-2 was higher (5.0+2.9sd) for the same isolates. Aspilia mossambicensis total extract and fractions-1,4 and 5 had mean IC50 values of 96.6+/-32.5,38.6+/-23.0,142.5+/-79.6 and >1250.0 microg/ml, respectively, against four P. falciparum isolates. These results show that fraction-1 of either A. gummifera or A, mossambicensis had the highest concentration of antimalarial principles. We now plan to concentrate our efforts on these promising fractions in order to isolate pure compounds which could eventually be used to effectively treat malaria.     

Antiplasmodial activity of alkaloid extracts from Pavetta crassipes (K. Schum) and Acanthospermum hispidum (DC), two plants used in traditional medicine in Burkina Faso

In the course of the search for new antimalarial compounds, a study of plants traditionally used against malaria in Burkina Faso was made. An ethnobotanical study permitted the identification of plants currently used by the traditional healers and herbalists. Two plants among them were selected for further study: Pavetta crassipes (K. Schum) and Acanthospermum hispidum (DC). Alkaloid extracts of these plants were tested in vitro against two reference clones of Plasmodium falciparum: the W2 chloroquine-resistant and the D6 chloroquine-sensitive strains. Significant inhibitory activity was observed with Pavetta crassipes (IC(50)=1.23 microg/ml) and A. hispidum (IC(50)=5.02 microg/ml). Antiplasmodial activity was also evaluated against six Plasmodium falciparum isolates from children between 4 and 10 years old. The IC(50) values for the alkaloid extracts were in the range 25-670 ng/ml. These results indicated that P. falciparum wild strains were more sensitive to the alkaloid extracts than strains maintained in continuous culture. Moreover, the alkaloid extracts exhibit good in vitro antimalarial activity and weak cytotoxicity against three human cell lines (THP1, normal melanocytes, HTB-66). Isolation and structural determination are now necessary in order to precisely determine the active compounds.     

Mangrove plants as a source of lead compounds for the development of new antiplasmodial drugs from South East coast of India

Malaria is the world's leading killer among the infectious diseases. The treatment of malaria is mystified by the challenges of widespread resistance of the malaria parasites to cheap and affordable antimalarial drugs. The present study was made in an attempt to identify the in vitro antiplasmodial activity against mangrove plant parts. (Avicennia marina, Acanthus ilicifolius, Bruguiera cylindrica, Excoecaria agallocha, Rhizophora apiculata, and Rhizophora mucronata mangrove plant extracts exhibited in vitro antiplasmodial activity against Plasmodium falciparum). Of the selected mangrove plant parts, the bark extract of A. marina exhibited minimum concentration of inhibitory activities IC(50) 49.63 μg.ml(-1). The leaf extract of A. marina, the hypocotyl extract of B. cylindrica, the leaf extract of E. agallocha, the flower extract of R. mucronata, and the hypocotyl extract of R. apiculata showed IC(50) values between 50 and 100 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 there were no morphological changes in erythrocytes by the ethanolic extract of mangrove plants after 48 h of incubation. The in vitro antiplasmodial activity might be due to the presence of alkaloids, carboxylic acids, coumarins, saponins, flavonoids, xanthoproteins, tannins, phenols, sugars, resins, steroids, and proteins in the ethanolic extracts of mangrove plants. It is concluded from the present study that the ethanolic extracts of mangrove plant parts of A. marina possess lead compounds for the development of antiplasmodial drugs.     

In vitro anti-plasmodial activity of some traditionally used medicinal plants against Plasmodium falciparum

The anti-plasmodial activity of different solvent extracts of Adhatoda vasica (root), Caesalpinia pulcherrima (leaf), Carica papaya (pulp), Erythroxylum monogynum (leaf), Lantana camara (whole plant), Ocimum sanctum (root) and Phyllanthus niruri (whole plant) were studied against Plasmodium falciparum. Of the 35 extracts tested, seven extracts showed good anti-plasmodial activity. Methanol extract of C. pulcherrima showed the lowest IC50 value (10.96 μg/mL) followed by methanol extract of A. vasica (IC(50)=11.1 μg/mL), chloroform extract of O. sanctum (IC(50)=11.47 μg/mL), methanol extract of E. monogynum (IC(50)=12.23 μg/mL), acetone extract of C. pulcherrima (IC(50)=12.49 μg/mL), methanol extract of O. sanctum and acetone extract of A. vasica (IC(50)=14.04 μg/mL). The results of the present study justify the use of these medicinal plants in traditional practice, and also, a further study on the isolation of anti-plasmodial molecules from their active crude extracts is in progress.     

A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue

Efforts to move from malaria control to eradication will require new approaches to block malaria transmission, such as the development of anti-malarial drugs with gametocytocidal activity. Here fluorescent oxidoreduction indicator alamarBlue is used to develop a screen for gametocyte viability. The fluorescent signal increases linearly with gametocyte number (R(2)=0.99) and determination of the IC(50) of epoxomicin demonstrated the assay was reproducible and sensitive (IC(50) 2.16±0.57 nM, Z'-factor 0.81±0.01). Six anti-malarials were also tested and at 10 μM only primaquine and dihydroartemisinin (DHA) had gametocytocidal activity. This new assay provides an important tool to efficiently screen compounds for gametocytocidal activity.     

In vitro activity of extracts and isolated polyphenols from West African medicinal plants against Plasmodium falciparum

The aim of the study was to screen 11 selected traditional medicinal plants from West Africa for their in vitro antiplasmodial activity in order to determine the activity of single and of combination of plant extracts and to examine the activity of isolated pure compounds. Ethanolic and aqueous extracts of the 11 selected plants and pure compounds from Phyllanthus muellerianus and Anogeissus leiocarpus were tested in vitro against Plasmodium falciparum 3D7. Proliferation inhibitory effects were monitored after 48 h. Among the plants and pure compounds investigated in this study, geraniin from P. muellerianus, ellagic, gentisic, and gallic acids from A. leiocarpus, and extracts from A. leiocarpus, P. muellerianus and combination of A. leiocarpus with P. muellerianus affected the proliferation of P. falciparum most potently. Significant inhibitory activity was observed in combination of A. leiocarpus with P. muellerianus (IC(50)?=?10.8 μg/ml), in combination of A. leiocarpus with Khaya senegalensis (IC(50)?=?12.5 μg/ml), ellagic acid (IC(50)?=?2.88 μM), and geraniin (IC(50)?=?11.74 μM). In general growth inhibition was concentration-dependent revealing IC(50) values ranging between 10.8 and -40.1 μg/ml and 2.88 and 11.74 μM for plant extracts and pure substances respectively. Comparison with literature sources of in vivo and in vitro toxicity data revealed that thresholds are up to two times higher than the determined IC(50) values. Thus, the present study suggests that geraniin from P. muellerianus; ellagic acid, gallic acid, and gentisic acid from A. leiocarpus; and combination of extracts from A. leiocarpus with either P. muellerianus or K. senegalensis could be a potential option for malaria treatment.     

In vitro antimalarial activity of traditionally used Western Ghats plants from India and their interactions with chloroquine against chloroquine-resistant Plasmodium falciparum

Malaria is a major global public health problem, and the alarming spread of drug resistance and limited number of effective drugs now available underline how important it is to discover new antimalarial compounds. An ethnopharmacological investigation was undertaken on Western Ghats plants traditionally used to treat malaria in India; 50 plants were very carefully selected from a total of 372 plants, and 200 extracts were prepared and tested for in vitro antiplasmodial activity alone and in combination with chloroquine (CQ) against CQ-resistant Plasmodium falciparum (strain MRC-Pf-43). In in vitro antiplasmodial activity, when plant extract alone is used, 29 extracts (or 14.5%) showed significant high in vitro antiplasmodial activity with IC₅₀ values ranging from 3.96 to 4.85 μg/ml, 53 extracts (or 26.5%) showed significant good in vitro antiplasmodial activity with IC₅₀ values ranging from 5.02 to 9.87 μg/ml, and 28 extracts (or 14%) showed significant moderate in vitro antiplasmodial activity with IC₅₀ values ranging from 10.87 to 14 μg/ml, respectively. In combination with CQ, 103 extracts (or 51.5%) showed significant synergistic in vitro antiplasmodial activities with synergistic factor values ranging from 1.03 to 1.92, and these activities were up to a fold higher with CQ, suggesting synergistic interactions of the two drugs. Our investigation has confirmed that above 62.1% of the plant extracts showed moderate to high in vitro antiplasmodial activity when used alone, and in combination with CQ, 55.7% of the extracts showed borderline to good synergistic activity.     

Synthesis and biological evaluation of 2-, 3-, and 4-acylaminocinnamyl-N-hydroxyamides as novel synthetic HDAC inhibitors

A new series of 2-, 3-, and 4-acylaminocinnamyl-N-hydroxyamides 1-3 have been prepared, and their anti-HDAC (against maize HD2, HD1-B, and HD1-A enzymes) activities have been assessed. Cinnamyl-hydroxyamides bearing acylamino substituents at the C2 position of the benzene ring (compounds 1a-g) showed very low HDAC inhibiting activities, with IC(50) values in the high micromolar range. By shifting the same acylamino groups from C2 to C3 (compounds 2a-g) as well as C4 (compounds 3a-f) position of the benzene ring, a number of highly potent HDAC inhibitors have been obtained. In the anti-HD2 assay 3c (IC(50) = 11 nM) was the most potent compound, being >11600-, 4.5-, and 10-fold more potent than sodium valproate, SAHA, and HC-toxin, respectively, and showing the same activity as trapoxin. HD1-B and HD1-A assays have been performed to screen the inhibitory action of 1-3 against mammalian class I (HD1-B) and class II (HD1-A) HDAC homologous enzymes. From the corresponding IC(50) data, a selectivity ratio has been calculated. In general, compounds 1-3 showed no or little selectivity towards the class II homologue HD1-A, the most selective being 2a with class II selectivity ratio = 4.3. About the inhibitory potency, the 4-(2-naphthoylamino)cinnamyl-N-hydroxyamide 3f showed the highest inhibiting effect against the two enzymes (IC(50-HD1-B) = 36 nM; IC(50-HD1-A) = 42 nM). Selected 2 and 3 compounds will be evaluated to determine their antiproliferative and cyto differentiating activities on HL-60 cells.     

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents

BACKGROUND: The continued endeavour to design novel, non-detergent molecules that can be useful as topical, prophylactic contraceptives has led to the discovery of substituted isoxazolecarbaldehydes as a new class of compounds exhibiting both spermicidal and acrosin inhibitory activities simultaneously. METHODS: Normal human semen samples were used to detect the spermicidal and acrosin inhibitory activities of the new compounds. Lactobacillus, HeLa and Candida cultures were used to determine the safety of compounds towards normal vaginal flora, their cytotoxicity and anti-fungal activity. Supravital staining and the hypo-osmotic swelling test (HOST) were used to detect the effect on sperm membrane integrity. Nonoxynol-9 (N-9) was used as a reference standard. RESULTS: The 5- and 3-substituted isoxazolecarbaldehydes showed significant spermicidal [minimum effective concentration (MEC)=0.005-2.5%] and acrosin inhibitory (IC50=3.9-58 x 10(-4) mol/l) activities in several molecules along with weak fungicidal activity against Candida albicans. Lineweaver-Burk and Dixon plot analysis of a representative structure showed non-competitive inhibition of human acrosin enzyme, and the most potent acrosin inhibitors also considerably diminished the induction of the acrosome reaction by Ca2+ ionophore. Some compounds were found to be significantly safer than N-9 towards Lactobacillus acidophilus in vitro at their respective spermicidal MECs. In the cytotoxicity assay, the IC50 of these compounds towards the HeLa cell line was of the same order as N-9 (0.9-0.1 mmol/l); however, in contrast, the compounds exhibited only a moderate effect on sperm membrane integrity. CONCLUSIONS: This study indicates that 5- and 3-substituted isoxazolecarbaldehydes are 'first generation' multifunctional, spermicidal molecules that hold promise for development as topical contraceptives with useful associated activities that can add considerably to their effectiveness, safety and prophylaxis.     

Design, synthesis, and preliminary evaluation of new pyrrolidine derivatives as neuraminidase inhibitors

A series of pyrrolidine derivatives were designed and synthesized in good yields starting from commercially available 4-hydroxy-L-proline using a suitable synthetic strategy. And their ability to inhibit neuraminidase was evaluated. These compounds showed potent inhibitory activity against influenza A (H3N2) neuraminidase. Within this series, four compounds, 6e, 9c, 9f and 10e, have the good potency (IC(50)=1.56 approximately 2.40microM) which is compared to the NA inhibitor oseltamivir (IC(50)=1.06microM), and could be used as lead compound in the future.     

Syntheses, urease inhibition, and antimicrobial studies of some chiral 3-substituted-4-amino-5-thioxo-1H,4H-1,2,4-triazoles

Chiral 3-substituted-4-amino-5-thioxo-1H,4H-1,2,4-triazoles (5a-i) were synthesized. The target molecules were prepared by cyclization of the corresponding dithiocarbazinic acids, obtained from hydrazides, in the presence of hydrazine hydrate. The chiral hydrazides were in turn synthesized form L-amino acids. The structures of all the compounds were confirmed by modern spectroscopic techniques and purity ascertained by elemental analysis. The synthesized compounds 5a-i were evaluated for urease inhibition and found to exhibit varying degrees of urease inhibition activity showing IC(50) values ranging from 22.0 +/- 0.5 to 43.8 +/- 0.3 microM. Compound 5b was found to be the most active, exhibiting IC(50) = 22.0 +/- 0.5 microM comparable to the standard, thiourea (IC(50) = 21.0 +/- 0.1 microM). Triazoles 5a-i were also screened for their antimicrobial properties and promising antibacterial activities were observed against five pathogenic bacteria. However, all the compounds were devoid of any antifungal activity.     

In vivo antimalarial evaluation of MAMA decoction on Plasmodium berghei in mice

The use of decoctions of different plant materials is common practice in antimalarial ethnomedicine in Africa. Scientific evaluation of such herbal combinations to verify the claims is important. The study has evaluated the antimalarial efficacy of MAMA decoction (MD), a multicomponent herbal preparation and its individual plant components, namely leaves of Morinda lucida Benth [Rubiaceae] (ML), Azadirachta indica A. Juss [Meliaceae] (AI), Alstonia boonei De Wild [Apocynaceae] (AB) and Mangifera indica L [Anacardiaceae] (MI) in Plasmodium berghei-infected mice. Each decoction was prepared by boiling the powdered leaf in water, concentrated in vacuo and freeze-dried. The acute toxicity of MD (LD₅₀?=?3.8 g/kg) was determined using Lorke's method. The antimalarial activities of MD and its plant components were evaluated by oral administration of the freeze-dried extracts (15–240 mg/kg) using the early malaria infection test model. The established malaria infection test was used to evaluate MD (60–240 mg/kg) while amodiaquine [10 mg/kg] (AQ) and distilled water were employed as the positive and negative controls, respectively. From the early malaria infection test, the effective doses at 50 % (ED₅₀) and 90 % (ED₉₀) for MD, AB, AI, ML, MI and AQ were 43, 79, 140, 134, 208 and 3.9 mg/kg and 202, 276, 291, 408, 480 and 9.2 mg/kg, respectively. For the established infection test, MD (240 mg/kg) and AQ gave parasite clearance of 55 and 95 % on day 5 of treatment. MD possesses antimalarial activity and is relatively safe.     

The importance of aspartate aminotransferase for platelet aggregation

In bovine platelets aspartate aminotransferase has a high activity. The enzyme in vitro is inhibited in a dose dependent manner by aminooxyacetate (IC50 = 10(-4) M), hydroxylamine (IC50 = 10(-4) M), and cycloserine (IC50 = 5 X 10(-3). The inhibitory effect of all the three compounds is strongest at low substrate (aspartate) concentration. Blocking of aspartate aminotransferase activity by these compounds in intact platelets is accompanied by the inhibition of ADP and collagen-induced aggregation. Among the three compounds the strongest inhibitor of platelet aggregation was hydroxylamine, which was also the most effective inhibitor of aspartate aminotransferase. Other metabolic blockers, i.e. dinitrophenol (DNP), rotenone and antimycin also inhibited the aggregation of platelets, and a synergism has been demonstrated between DNP, rotenone and antimycin A action on platelet aggregation and blockade of aspartate aminotransferase activity. The results are interpreted to mean that transamination is of importance in the energy production in the activated platelet, probably through its participation in reducing equivalents transport from the cytosol to the mitosol via the malate: oxaloacetate: aspartate shuttle.     

Antimalarial activities of medicinal plants and herbal formulations used in Thai traditional medicine

Malaria is one of the world's leading killer infectious diseases with high incidence and morbidity. The problem of multidrug-resistant Plasmodium falciparum has been aggravating particularly in Southeast Asia. Therefore, development of new potential antimalarial drugs is urgently required. The present study aimed to investigate antimalarial activities of a total of 27 medicinal plants and 5 herbal formulations used in Thai traditional medicine against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) P. falciparum clones. Antimalarial activity of the ethanolic extracts of all plants/herbal formulations against K1 and 3D7 P. falciparum clones was assessed using SYBR Green I-based assay. All plants were initially screened at the concentration of 50 μg/ml to select the candidate plants that inhibited malaria growth by ≥50 %. Each candidate plant was further assessed for the IC₅₀ value (concentration that inhibits malaria growth by 50 %) to select the potential plants. Selectivity index (SI) of each extract was determined from the IC₅₀ ratio obtained from human renal epithelial cell and K1 or 3D7 P. falciparum clone. The ethanolic extracts from 19 medicinal plants/herbal formulation exhibited promising activity against both K1 and 3D7 clones of P. falciparum with survival of less than 50 % at the concentration of 50 μg/ml. Among these, the extracts from the eight medicinal plants (Plumbago indica Linn., Garcinia mangostana Linn., Dracaena loureiri Gagnep., Dioscorea membranacea Pierre., Artemisia annua Linn., Piper chaba Hunt., Myristica fragrans Houtt., Kaempferia galanga Linn.) and two herbal formulations (Benjakul Formulation 1 and Pra-Sa-Prao-Yhai Formulation) showed potent antimalarial activity with median range IC₅₀ values of less than 10 μg/ml against K1 or 3D7 P. falciparum clone or both. All except G. mangostana Linn. and A. annua Linn. showed high selective antimalarial activity against both clones with SI?>?10. Further studies on antimalarial activities in an animal model including molecular mechanisms of action of the isolated active moieties are required.     

An open study to evaluate the efficacy of artemether in severe falciparum malaria

An open clinical trial was conducted in 30 patients of severe falciparum malaria with heavy parasitaemia (parasitized erythrocytes above 5%). Artemether (methyl ether of dihydroartemisinin-active principle isolated from Chinese plant Qinghaosu) was administered as 80 mg intramuscular injection twice on first day and then single dose of 80 mg intramuscular on 2nd to 5th day. The trial could be completed in 28 patients and two patients expired. In our observation falciparum malaria affected the young adults in their most productive period of life i.e. 25-44 yrs. All patients became afebrile by the 4th day with fever clearance time approximately 31.92 +/- 15.30 hr. Twenty-five patients (83.33%) became parasite free by 5th day with mean parasite clearance time approximately 47.04 +/- 19.95 hr. Deranged liver function and renal profile was observed in 63% and 50% patients respectively. Two patients, who died had very high degree of parasitaemia (50% and 16%) with cerebral malaria. One died due to multiorgan failure and other due to massive hematemesis and shock. The type of response achieved by artemether therapy was analysed as per WHO criteria suggested for chloroquine resistance. S response was observed in 25 patients (cure rate 83.33%). Two patients (6.66%) patients showed R II response, one patient (3.33%) showed R III response and R I response was not observed in any patient. No significant side effects were noted. This pilot study demonstrated that intramuscular artemether is a useful addition to antimalarial drugs in this era of multidrug resistant P. falciparum malaria showing high clinical potency with virtually no side effect.     

Antileishmanial and antimalarial chalcones: synthesis, efficacy and cytotoxicity of pyridinyl and naphthalenyl analogs

The antileishmanial and antimalarial activity of methoxy-substituted chalcones (1,3-diphenyl-2-propen-1-ones) is well established. The few analogs prepared to date where the 3-phenyl group is replaced by either a pyridine or naphthalene suggest these modifications are potency enhancing. To explore this hypothesis, sixteen 3-naphthalenyl-1-phenyl-2-prop-1-enones and ten 1-phenyl-3-pyridinyl-2-prop-1-enones were synthesized and their in vitro efficacies against Leishmania donovani and Plasmodium falciparum determined. One inhibitor with submicromolar efficacy against L. donovani was identified (IC50 = 0.95 microM), along with three other potent compounds (IC50 < 5 microM), all of which were 3-pyridin-2-yl derivatives. No inhibitors with submicromolar efficacy against P. falciparum were identified, though several potent compounds were found (IC50 < 5 microM). The cytotoxicity of the five most active L. donovani inhibitors was assessed. At best the IC50 against a primary kidney cell line was around two-fold higher than against L. donovani. Being more active than pentamidine, the 1-phenyl-3-pyridin-2-yl-2-propen-1-ones have potential for further development against leishmaniasis; however it will be essential in such a program to address not only efficacy but also their potential for toxicity.     

Anti-HIV-1 activity of antiviral compounds, as quantitated by a focal immunoassay in CD4+ HeLa cells and a plaque assay in MT-4 cells

The inhibitory effects of a series of antiviral compounds on human immunodeficiency virus type 1 (HIV-1) were evaluated in a plaque assay (PA) in MT-4 cells and a focal immunoassay (FIA) in CD4+ HeLa cells. Similar 50% inhibitory concentrations (IC50) were obtained for the sulfated polysaccharides when measured by PA or FIA: the IC50 values of dextran sulfate and pentosan polysulfate were 0.8 microgram/ml and 0.35 microgram/ml, respectively. Also, comparable IC50 values (ranging from 1.42 to 2.71 microM) were obtained for purine 2',3'-dideoxyribosides (i.e. DDA, DDI and DDG) when evaluated by PA or FIA. In contrast, the IC50 values of pyrimidine 2',3'-dideoxyribosides were invariably 4- to 10-fold lower when monitored by PA than FIA: the IC50s of AZT, D4T and DDC in the PA were 0.015, 0.094 and 0.038 microM, respectively, and in the FIA were 0.062 microM, 0.29 microM and 0.46 microM, respectively. The differential anti-HIV-1 activities found with AZT, D4T and DDC in the PA and FIA systems may at least be related in part to differences in the metabolism of the compounds (i.e. phosphorylation by thymidine kinase or 2'-deoxycytidine kinase) between MT-4 and CD4+ HeLa cells. The novel anti-HIV-1 compounds tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO) derivatives, R82150 and R82913, and the acyclouridine derivative 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT) were also more inhibitory to HIV-1 in the PA than FIA system. The IC50 values of R82150, R82913 and HEPT, as based on PA, were 0.005, 0.003 and 0.79 microM, respectively. Their IC50 values, as based on FIA, were 0.020 microM, 0.015 microM and 3.77 microM, respectively. The TIBO derivatives emerged as the most effective HIV-1 inhibitors of the compounds tested whether assayed by PA or FIA.     

Antimicrobial and antioxidant activities of the extracts and compounds from the leaves of Psorospermum aurantiacum Engl and Hypericum lanceolatum Lam

ABSTRACT: BACKGROUND: Psorospermun aurantiacum and Hypericum lanceolatum are plants locally used in Cameroon and other parts of Africa for the treatment of gastrointestinal and urinary tract infections, skin infections, venereal diseases, gastrointestinal disorder, infertility, epilepsy as well as microbial infections. The present study was designed in order to investigate the in vitro antimicrobial and radical scavenging activities of the extracts and isolated compounds from the leaves of these plants. METHODS: The plant extract was prepared by maceration in methanol and fractionated by column chromatography. The structures of isolated compounds were elucidated by spectroscopic analyses in conjunction with literature data. The broth microdilution method was used to evaluate the in vitro antimicrobial activity against bacteria, yeasts and dermatophytes. The antioxidant potentials of the extracts and their isolated compounds were evaluated using the DPPH radical scavenging method. RESULTS: Five known compounds: physcion (1), 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (2), kenganthranol B (3), vismiaquinone (4), octacosanol (5) were isolated from the leaves of P. aurantiacum while six compounds including friedelin (6), betulinic acid (7), 2,2',5,6'-tetrahydroxybenzophenone (8), allanxanthone A (9), 1,3,6- trihydroxyxanthone (10) and isogarcinol (11) were isolated from H. lanceolatum. Compound 8 and 4 exhibited the highest antibacterial and antifungal activities with MIC ranges of 2--8 mug/ml and 4--32 mug/ml respectively. P. aurantiacum crude extract (Rsa50 = 6.359 [PLUS-MINUS SIGN] 0.101) showed greater radical scavenging activity compared with H. lanceolatum extract (Rsa50 = 30.996 [PLUS-MINUS SIGN] 0.879). Compound 11 showed the highest radical scavenging activity (RSa50 = 1.012 [PLUS-MINUS SIGN] 0.247) among the isolated compounds, comparable to that of L-arscobic acid (RSa50 = 0.0809 [PLUS-MINUS SIGN] 0.045). CONCLUSIONS: The experimental findings show that the methanol extract and isolated compounds from P. aurantiacum and H. lanceolatum stem bark possess significant antimicrobial and antioxidant activities justifying the use of these plants in traditional medicine, which may be developed as phytomedicines.     

Vismione H and structurally related anthranoid compounds of natural and synthetic origin as promising drugs against the human malaria parasite Plasmodium falciparum: structure-activity relationships

Natural and synthetic anthranoid compounds were subjected to an evaluation against asexual erythrocytic stages of the human malaria parasite Plasmodium falciparum in vitro. Stimulated by the good activities of Vismia guineënsis extracts, a more detailed investigation of the active principles revealed the prenylated preanthraquinone vismione H (1) to be a potent antimalarial [50% growth-inhibitory concentration (IC₅₀) 0.088?μg/ml]. On the basis of this finding a series of chemically related phlegmacins (2–5), flavomannins (6–8), and rufoolivacins (9–11) isolated from several species of Cortinarius, a genus of higher fungi, and 5 synthetic vismione-like anthranoids (12–16) were evaluated as well. Although these compounds displayed weaker antiplasmodial effects than did vismione H (1) itself, considerable levels of activity were obtained with phlegmacin B₁ (2), flavomannin-6,6′-di-O-methyl ether A₁ (6), trans-4-hydroxy-flavomannin-6,6′-di-O-methyl ether A (8), and rufoolivacin B (10). Initial preconditions for activity within the vismiones and related anthranoids were established.     

Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization.

The mechanism of Ca2+ sensitization of contraction has not been elucidated in airway smooth muscle (SM). To determine the role of a small G protein, rhoA p21, and its target protein, rho-associated coiled coil-forming protein kinase (ROCK), in receptor-coupled Ca2+ sensitization of airway SM, we studied the effect of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexane carboxamide dihydrochloride, monohydrate (Y-27632), a ROCK inhibitor, on isometric contractions in rabbit tracheal and human bronchial SM. Y-27632 completely reversed 1 microM carbachol (CCh)-induced contraction of intact trachea with a concentration producing half-maximum inhibition of effect (IC50) of 1.29 +/- 0.2 microM (n = 5). Although 4beta-phorbol 12,13-dibutyrate (1 microM)-induced Ca2+ sensitization was relatively resistant to Y-27632 in alpha-toxin-permeabilized trachea, CCh (100 microM) plus guanosine triphosphate (GTP) (3 microM)- and guanosine 5'-O-(3'-thiotriphosphate) (10 microM)-induced contractions were relaxed completely by Y-27632 with IC50 of 1.44 +/- 0.3 (n = 6) and 1.15 +/- 0.3 microM (n = 6). Endothelin-1 (1 microM) plus GTP (3 microM)- developed force was also reversed by Y-27632 with IC50 of 4. 10 +/- 1.1 microM (n = 6) in the alpha-toxin-permeabilized bronchus. Both the rabbit and human SM expressed rhoA p21, ROCK I, and its isoform ROCK II. Collectively, rho/ROCK-mediated Ca2+ sensitization plays a central role in the sustained phase of airway SM contraction, and selective inhibition of this pathway may become a new strategy to resolve airflow limitation in asthma.