Anti-Shigella and antioxidant-based screening of some Cameroonian medicinal plants, UHPLC-LIT-MS/MS fingerprints, and prediction of pharmacokinetic and drug-likeness properties of identified chemicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Shigella infection is a public health problem responsible for approximately 700,000 deaths annually. The management of this disease is impaired by the emergence of multidrug-resistant Shigella species, highlighting the urgent need to search for alternative treatment options. In this regard, investigating medicinal plants traditionally used for the treatment of dysentery, diarrheal infections, and/or associated symptoms in endemic regions might provide an opportunity to identify phytochemicals that could be further used as a basis for the development of future anti-shigella drug candidates. AIM OF THE STUDY: This study was designed to investigate the anti-shigella and antioxidant-based ethnopharmacological potency of some Cameroonian medicinal plants with an emphasis on pharmacokinetic properties of the identified chemical pharmacophore. MATERIALS AND METHODS: Briefly, plant species were selected and collected based on their ethnopharmacological uses and information reported in the literature. Crude aqueous, ethanolic, methanolic, and hydroethanolic (30:70, v/v) extracts from these plants were prepared and then screened for their anti-Shigella activity against four Shigella strains and cytotoxicity against Vero and Raw cell lines using microdilution and resazurin-based methods, respectively. The antioxidant activities of potent extracts were evaluated using DPPH, ABTS, NO, and FRAP scavenging assays. The chemical profile of potent extracts was performed using the UHPLC-LIT-MS/MS and the pharmacokinetic properties, druglikeness, and likely molecular targets of the chemical scaffolds identified were predicted using SwissADME and SwissTargetPredictor. RESULTS: Thirty-nine (39) plants belonging to 26 plant families were harvested. Out of the 228 extracts tested, 18 extracts originating from 6 plants (15.38 %) were active (MICs 250-1000 µg/mL) and nontoxic toward Vero (CC50 129.25-684.55 µg/mL) and Raw cell lines (CC50 336.20 to >1000 µg/mL). Six potent extracts from the two plants exhibited moderate to potent DPPH (SC50 8.870-54.410 µg/mL), ABTS (SC50 12.020-27.36 µg/mL), and NO (SC50 0.02-195.85 µg/mL) scavenging activities. Later, these extracts showed interesting ferric iron-reducing power (1.28-12.14 µg equivalent NH2OH/g of extract). The shortest onset of action time (4 and 6 h) observed following inhibition kinetics studies was observed with extracts BFSHE, PMSE, and PMSM. The UHPLC-LIT-MS/MS and some databases (Mass Spectral Library (NIST 14), Human Metabolome Database (HMD), MassBank, SuperNatural 3.0, The Food Database (FooDB), and Chemical Entities of Biological Interest (ChEBI)) allowed the annotation of 18 and 17 metabolites in the extracts from stem bark of P. macrophylla and B. ferruginea respectively. Pharmacokinetic prediction of these chemicals showed that compound 6 (4,6a-bis(Hydroxymethyl)-9a-methyl-3-oxo-1a,1b,3,5,6,6a,7a,9a-octahydrobis (oxireno)[2',3':5,6; 2″,3'':9,10]cyclodeca[1,2-b]furan-5-yl methacrylate), compound 8 (Corynoxeine), and compounds 35 (Stachybotrydial acetate) demonstrated acceptable druglike and pharmacokinetic properties and might act through inhibition of kinase, transferase, protease, oxidoreductase, and family AG protein-linked receptors. CONCLUSION: The findings from this investigation demonstrated that Cameroonian medicinal plants are suitable reservoirs of anti-Shigella and antioxidant agents with good drug candidate properties.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

Foetidumins A-D, and other chemical constituents from Helichrysum foetidum (L.) Moench (Asteraceae) with antiparasite activity.

The phytochemical investigation of the MeOH and CH2Cl2-MeOH (1:1) extracts from the flowers and twigs of Helichrysumfoetidum (L.) Moench (Asteraceae), which showed antileishmanial and antiplasmodial activities during the preliminary screening, led to the isolation of four undescribed compounds, including two ent-beyer-15-ene-type diterpenoids, foetidumins A (1) and B (2), one flavonoid, foetidumin C (3) and one chalcopyrone, foetidumin D (4). Additionally, fourteen known compounds comprising, two ent-beyer-15-ene-type diterpenoids (5-6), six flavonoids (7-12), two steroids (13-14), three triterpenoids (15-17), and one glyceryl monostearate (18) were also isolated. The chemical structures of foetidumins A-D were fully elucidated by analyses of their spectroscopic data. The structure and the stereochemistry of foetidumin A (1) were confirmed by SC-XRD analyses. Among the tested compounds, foetidumin C (3), erythroxylol A (6), and kaempferol (7) displayed the highest antileishmanial potency with IC50 values of 13.0, 11.8, and 11.1 µM, respectively. Foetidumin C (3) had no cytotoxicity toward Vero cells with the selectivity index > 3.59. Meanwhile, extracts of flowers and twigs had higher activity against Plasmodium falciparum chloroquine-sensitive (Pf3D7) strain with IC50 values of 3.66 and 10.52 µg/mL, respectively.

Antileishmanial and Antiplasmodial Activities of Secondary Metabolites from the Root of Antrocaryon klaineanum Pierre (Anacardiaceae).

Antrocaryon klaineanum is traditionally used for the treatment of back pain, malaria, female sterility, chlamydiae infections, liver diseases, wounds, and hemorrhoid. This work aimed at investigating the bioactive compounds with antileishmanial and antiplasmodial activities from A. klaineanum. An unreported glucocerebroside antroklaicerebroside (1) together with five known compounds (2-6) were isolated from the root barks of Antrocaryon klaineanum using chromatographic techniques. The NMR, MS, and IR spectroscopic data in association with previous literature were used for the characterization of all the isolated compounds. Compounds 1-4 are reported for the first time from A. klaineanum. The methanol crude extract (AK-MeOH), the n-hexane fraction (AK-Hex), the dichloromethane fraction (AK-DCM), the ethyl acetate fraction (AK-EtOAc), and compounds 1-6 were all evaluated for their antiparasitic effects against Plasmodium falciparum strains susceptible to chloroquine (3D7), resistant to chloroquine (Dd2), and promastigotes of Leishmania donovani (MHOM/SD/62/1S). The AK-Hex, AK-EtOAc, AK-MeOH, and compound 2 were strongly active against Dd2 strain with IC50 ranging from 2.78 ± 0.06 to 9.30 ± 0.29 µg/mL. Particularly, AK-MeOH was the most active-more than the reference drugs used-with an IC50 of 2.78 ± 0.06 µg/mL. The AK-EtOAc as well as all the tested compounds showed strong antileishmanial activities with IC50 ranging from 4.80 ± 0.13 to 9.14 ± 0.96 µg/mL.

Potentiation effect of mallotojaponin B on chloramphenicol and mode of action of combinations against Methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus, the causative agent of many infectious diseases has developed resistance to many antibiotics, even chloramphenicol which was the essential antibiotic recommended for the treatment of bacterial infection. Thus, other alternatives to fight against S. aureus infections are necessary; and combinatory therapy of antibiotics with natural compounds is one of the approaches. This study evaluated the activity of the combination of mallotojaponin B and chloramphenicol against Methicillin-resistant Staphylococcus aureus (MRSA). Antibacterial activities were evaluated by broth microdilution and the checkerboard methods. Modes of action as time-kill kinetic, Nucleotide leakage, inhibition and eradication of biofilm, and loss of salt tolerance were evaluated. Cytotoxicity was evaluated on Vero and Raw cell lines. Mallotojaponin B showed good activity against MRSA with a MIC value of 12.5 µg/mL. MRSA showed high resistance to chloramphenicol (MIC = 250 µg/mL). The combination produced a synergistic effect with a mean FICI of 0.393. This combination was bactericidal, inducing nucleotide leakage, inhibiting biofilm formation, and eradicating biofilm formed by MRSA. The synergic combination was non-cytotoxic to Vero and Raw cell lines. Thus, the combination of mallotojaponin B and chloramphenicol could be a potential alternative to design a new drug against MRSA infections.

Attitudes and Practices of the Use of Third-Generation Cephalosporins among Medical Doctors Practicing in Cameroon.

Background: Third-generation cephalosporins (3GC) are among the most prescribed antibiotics worldwide. Antibiotic resistance, usually due to misuse and overuse, is a feared complication of public health concern. However, there are limited data in Cameroon concerning the knowledge and use of 3GC in our health services. The aim of this study was to assess the knowledge and use of 3GC among medical doctors in Cameroon and to generate baseline information for a wider scale research and policy implementation. Methods: This study was a cross-sectional study conducted among medical doctors practicing in Cameroon in general. Convenience sampling was used and the data were collected from both the online questionnaire and the review of files of patients admitted and discharged within the month of April 2021 and analysed with the use of IBM SPSS v25. Results and Discussion. A total of 52 respondents from the online questionnaire and 31 reviewed files were retained. Of the respondents, 27% were female and 73% were male. The mean age and years of experience were 29.6 ± 2.9 and 3.6 ± 2.1 years, respectively. Only 32.7% had correct knowledge of the number of generations of cephalosporins, and 48.1% had knowledge of the antimicrobial target. All medical doctors (MD) identified ceftriaxone as a 3GC, and it was the most commonly prescribed 3GC (71%). Most of the MD considered 3GC to be an efficient antibiotic. Just over half (54.7%) knew the correct posology of ceftriaxone. Only 17% and 9.4% knew the right posology for cefotaxime and ceftazidime, respectively, for the management of early-onset neonatal infection (EONNI). The misuse of 3GC was mostly attributed to nurses, MD, and poor institutional policies. Conclusion: There is average knowledge on 3GC among MD, with ceftriaxone being the most widely known and prescribed. Misuse is common among nurses and doctors. Poor institutional policies and limited laboratory capacities are to be blamed.

Antibacterial and antishigellosis activity of Xylopia staudtii (engl. & diels), Annonaceae.

ETHNOPHARMACOLOGICAL RELEVANCE: Xylopia staudtii is a medicinal plant which fruits are traditionally used in western Cameroon as a spice in the preparation of soups known for their abdominal cramp relieving properties. Often identified as Xylopia africana, its bark is used in the treatment of dysentery in Mont Cameroun localities. This plant could therefore contain active ingredients against intestinal pathogens, including Shigella spp, which are responsible of the deathly dysenteric diarrhoea. AIM OF THE STUDY: This study aims to assess the efficacy of the hydroethanolic extract from Xylopia staudtii bark in immunodepressed mice infected with Shigella flexneri. MATERIALS AND METHODS: Qualitative detection of compounds in the crude extract was done using UPLC-DAD-(HR) ESI-MS analysis in an attempt to link the activity to the chemical composition. The MIC and the MBC of the extract was determined using broth dilution method. Shigellosis was induced by intraperitoneal administration of Shigella flexneri to immunodepressed mice pretreated with streptomycin. These infected mice were then treated with the extract (100, 200 and 400 mg/kg), and reference substances (ciprofloxacin and saline). During the 9 days of treatment, animal morphology, fecal pathology and deaths were recorded. At the end of the treatment period, blood and organs were collected from any surviving animals for hematological, biochemical and histopathological analyses. RESULTS: The extract was found to be significantly active, with a bactericidal effect against Shigella and a bacteriostatic effect against Escherichia coli. It was able to reduce and stop the faecal pathology caused by the infection in mice, as well as the rate of deaths which was brought to zero (0) in animal treated at 400 mg/kg. The bacteria load in faeces was reduced by 100% in animal treated at 400 mg/kg. Xylopia staudtii extract elicited anti-inflammatory properties by reducing MPO activity and Lcn2 intestinal level. It also prevents damages in the intestinal tissue and the shortening of colon which characterise Shigella infection. The serum level of ASAT, ALAT, bilirubin, urea and creatinine in animals treated with the extract was similar to those of normal animal used in the study. These activities of the plant may be due at least in part to the presence of ent-kauran type diterpens such as kaurenoic acid identified in the extract. CONCLUSION: These findings support the usage of Xylopia staudtii as an antimicrobial against bacillary dysentery, making this plant a potential candidate for the formulation of an improved standardized traditional medicine.

Arbuscular mycorrhizal fungi alter antifungal potential of lemongrass essential oil against Fusarium solani, causing root rot in common bean (Phaseolus vulgaris L.).

The variation in chemical composition of essential oils (EOs) as affected by plant phenology and environmental factors is a crucial limitation in standardization of EOs and thus their effective implementation into novel organic farming. The cultivation of medicinal and aromatic plants (MAP) using bio-elicitors has been advocated as genuine tool to sustainably assure higher quantity and quality EOs. Herein, a field trial and laboratory bioassays were undergone to decipher the impact of a local arbuscular mycorrhizal fungi (AMF) inoculation on agro-morphological yield, EO output and differential suppression of common bean (Phaseolus vulgaris L.) root rot incited by Fusarium solani. The field experiment was laid out following a completely randomized block design (CRBD) with two treatments; non-inoculated control and AMF-inoculation in triplicates. The effects of the EOs were tested against mycelial growth, conidia and common bean seeds germination. Promising concentrations were thereafter assessed for their suppressive effect against Fusariun solani in planta. A significantly higher collar diameter, hypocotyl branching and subsequent Mycorrhizal Dependency (MD) in mycorrhizal lemongrass [(+)AMF] compared to non-inoculated counterpart [(-)AMF]. The resulting EOs consistently repressed F. solani Fs4 conidia germination and mycelium deployment in a dose-dependent manner, with minimum inhibitory concentration (MIC) of 500 ppm for both the EOs, and 125 ppm for the reference fungicide (Ridomil Plus 44 WP). The EO from mycorrhizal lemongrass protected the common bean plantlets from infection by F. solani Fs4 both in laboratory and greenhouse conditions, leading to healthier and vigorous plantlets. The best protection rate was once more obtained with EO from AMF-primed lemongrass at the concentration of 1000 ppm (65.0%) while the lowest disease severity was obtained with Ridomil Plus 44 WP (63.13%). Overall, AMF inoculation shifted the lemongrass biochemical processes with subsequent impact on growth, and an enhanced suppression in Fusarium root rot under greenhouse conditions.

Garcinia kola (Heckel) and Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. from Cameroon possess potential antisalmonellal and antioxidant properties.

Drug resistant Salmonella species and shortcomings related to current drugs stress the urgent need to search for new antimicrobial agents to control salmonellosis. This study investigated the antisalmonellal and antioxidant potentials of methanolic and hydro-ethanolic extracts of Garcinia kola and Alchornea cordifolia as potential sources of drugs to control Salmonella species and to reduce related oxidative stress. The antisalmonellal activity was assessed using the broth microdilution, membrane destabilization and time-kill kinetic assays. While, the DPPH, ABTS and FRAP assays were used for the determination of the antioxidant activities. The minimum inhibitory concentrations ranged from 125 to 1000 µg/mL, with the methanolic root extract of G. kola being the most active. The time kill kinetic assay revealed a concentration-dependent bacteriostatic activity for promising extracts. Potent extracts from G. kola showed the ability to destabilize S. typhi outer membrane, with the methanolic root extract presenting the highest activity; two-fold higher than those of polymyxin B tested as reference. In addition, this methanolic root extract of G. kola also provoked nucleotide leakage in a concentration-dependent manner. From the antioxidant assays, the hydro-ethanolic extract from the stem bark of A. cordifolia presented significant activities comparable to that of Vitamin C. The methanolic root extract of G. kola also presented appreciable antioxidant activities, though less than that of A. cordifolia. Overall, the phytochemical screening of active extracts revealed the presence of anthocyanins, flavonoids, glycosides, phenols, tannins, triterpenoids and steroids. These results provide evidence of the antibacterial potential of G. kola and offer great perspectives in a possible standardisation of an antisalmonellal phytomedicine.

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei.

BACKGROUND: Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. OBJECTIVES: The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. MATERIALS AND METHODS: Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. RESULTS: Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 µg/mL to 5.886 µg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50 = 0.809 µg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. CONCLUSION: The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity.

Anti-Plasmodium falciparum Activity of Extracts from 10 Cameroonian Medicinal Plants.

Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated by fake medications or the use of single drugs has worsened the situation, thereby emphasizing the need for a continued search for potent, safe, and affordable new antimalarial treatments. In line with this need, we have investigated the antiplasmodial activity of 66 different extracts prepared from 10 different medicinal plants that are native to Cameroon. Methods: Extracts were evaluated for their capacity to inhibit the growth of the chloroquine-sensitive (Pf3D7) and resistant (PfINDO) strains of P. falciparum using the SYBR green fluorescence method. The cytotoxicity of promising extracts against human embryonic kidney cells (HEK293T) mammalian cells was assessed by MTT assay. Results: The antiplasmodial activity (50% inhibitory concentration, IC50) of plant extracts ranged from 1.90 to >100 µg/mL against the two strains. Six extracts exhibited good activity against both Pf3D7 and PfINDO strains, including cold water, water decoction, and ethyl acetate extracts of leaves of Drypetes principum (Müll.Arg.) Hutch. (IC503D7/INDO = 4.91/6.64 µg/mL, 5.49/5.98 µg/mL, and 6.49/7.10 µg/mL respectively), water decoction extract of leaves of Terminalia catappa L. (IC503D7/INDO = 6.41/8.10 µg/mL), and water decoction extracts of leaves and bark of Terminalia mantaly H.Perrier (IC503D7/INDO = 2.49/1.90 µg/mL and 3.70/2.80 µg/mL respectively). These promising extracts showed no cytotoxicity against HEK293T up to 200 µg/mL, giving selectivity indices (SIs) in the range of >31.20⁻80.32. Conclusions: While providing credence to the use of D. principum, T. catappa, and T. mantaly in the traditional treatment of malaria, the results achieved set the stage for isolation and identification of active principles and ancillary molecules that may provide us with new drugs or drug combinations to fight against drug-resistant malaria.

Marine Algae as Source of Novel Antileishmanial Drugs: A Review.

Leishmaniasis is a vector-borne neglected tropical disease caused by protozoan parasites of the Leishmania genus and transmitted by the female Phlebotomus and Lutzomyia sand flies. The currently prescribed therapies still rely on pentavalent antimonials, pentamidine, paromomycin, liposomal amphotericin B, and miltefosine. However, their low efficacy, long-course treatment regimen, high toxicity, adverse side effects, induction of parasite resistance and high cost require the need for better drugs given that antileishmanial vaccines may not be available in the near future. Although most drugs are still derived from terrestrial sources, the interest in marine organisms as a potential source of promising novel bioactive natural agents has increased in recent years. About 28,000 compounds of marine origin have been isolated with hundreds of new chemical entities. Recent trends in drug research from natural resources indicated the high interest of aquatic eukaryotic photosynthetic organisms, marine algae in the search for new chemical entities given their broad spectrum and high bioactivities including antileishmanial potential. This current review describes prepared extracts and compounds from marine macroalgae along with their antileishmanial activity and provides prospective insights for antileishmanial drug discovery.

In Vitro Activity of Selected West African Medicinal Plants against Mycobacterium ulcerans Disease.

Buruli ulcer (BU) is the third most prevalent mycobacteriosis, after tuberculosis and leprosy. The currently recommended combination of rifampicin-streptomycin suffers from side effects and poor compliance, which leads to reliance on local herbal remedies. The objective of this study was to investigate the antimycobacterial properties and toxicity of selected medicinal plants. Sixty-five extracts from 27 plant species were screened against Mycobacterium ulcerans and Mycobacterium smegmatis, using the Resazurin Microtiter Assay (REMA). The cytotoxicity of promising extracts was assayed on normal Chang liver cells by an MTT assay. Twenty five extracts showed activity with minimal inhibitory concentration (MIC) values ranging from 16 µg/mL to 250 µg/mL against M. smegmatis, while 17 showed activity against M. ulcerans with MIC values ranging from 125 µg/mL to 250 µg/mL. In most of the cases, plant extracts with antimycobacterial activity showed no cytotoxicity on normal human liver cells. Exception were Carica papaya, Cleistopholis patens, and Polyalthia suaveolens with 50% cell cytotoxic concentrations (CC50) ranging from 3.8 to 223 µg/mL. These preliminary results support the use of some West African plants in the treatment of Buruli ulcer. Meanwhile, further studies are required to isolate and characterize the active ingredients in the extracts.

Anti-plasmodial and cholinesterase inhibiting activities of some constituents of Psorospermum glaberrimum.

Glaberianthrone (1), a new bianthrone was isolated from the hexane extract of the stem bark of Psorospermum glaberrimum together with thirteen known compounds: 3-geranyloxyemodin anthrone (2), friedelan-3-one (3), 3-prenyloxyemodin anthrone (4), 3-geranyloxyemodin (5), 3-prenyloxyemodin (6), friedelan-3-ol (7), acetylvismione D (8), betulinic acid (9), 2-geranylemodin (10), bianthrone A2b (11), bianthrone 1a (12), emodin (13) and 2-prenylemodin (14). The structures of the isolated compounds were established by means of spectroscopic methods. The extracts and the isolated compounds were tested in vitro for their anti-plasmodial activity against Plasmodium falciparum (chloroquine resistant strain W2) and for their acetyl- and butyrylcholinesterase inhibitory properties. The n-hexane extract showed good anti-plasmodial activity against P. falciparum W2 strain, with IC(50) of 0.87 microg/ml. It also exhibited 65.5% and 98.2% of acetyl- and butyrylcholinesterase inhibition at 0.2 mg/ml, respectively. Compounds 2 and 8 showed the best potencies against P. falciparum W2 strain with IC(50) of 1.68 microM and 0.12 microM, (0.66 microg/ml and 0.054 microg/ml) respectively. All tested compounds showed good butyrylcholinesterase inhibition activities with compound 12 displaying the best potency (IC(50) 9.25+/-0.25 microM). All the tested compounds showed weak inhibitory activity against acetylcholinesterase.

Anti-plasmodial activity of some constituents of the root bark of Harungana madagascariensis LAM. (Hypericaceae).

Bazouanthrone (1), a new anthrone derivative, has been isolated from the root bark of Harungana madagascariensis, together with known compounds, feruginin A (2), harunganin (3), harunganol A (4), harunganol B (5), friedelan-3-one (6) and betulinic acid (7). The structure of the compound (1) was assigned as 3,5,8,9-tetrahydroxy-2,4,4-tri-(3,3-dimethylallyl)-6-methyl-1-(4H)-anthracenone, by means of spectroscopic analysis. The anti-plasmodial activity of the isolated compounds was evaluated in culture against W2 strain of Plasmodium falciparum. All the compounds were found to be active against the Plasmodium parasites with bazouanthrone (1) showing particular potency (IC50=1.80 microM).