Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae).

The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4-15). In addition, four new derivatives (11a-11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 µM.

In vitro antimicrobial and anti-proliferative activities of plant extracts from Spathodea campanulata, Ficus bubu, and Carica papaya.

CONTEXT: African medicinal plants represent a prominent source of new active substances. In this context, three plants were selected for biological investigations based on their traditional uses. OBJECTIVE: The antimicrobial and anti-proliferative features of three plants used for medicinal purpose were evaluated. MATERIALS AND METHODS: The antimicrobial activities of methanol extracts of Ficus bubu Warb. (Moraceae) stem bark and leaves, of Spathodea campanulata P. Beauv. (Bignoniaceae) flowers, as well as those of Carica papaya Linn. (Caricaceae) latex, were determined using the microbroth dilution method against a set of bacteria and fungi pathogens including: Enterococcus faecalis, Staphylococcus aureus, S. saprophyticus, S. epidermididis, Escherichia coli, Klebsiella pneumonia, Salmonella typhimurium, Candida albicans, and Trichophyton rubrum. The tested concentrations of extracts ranged from 2500.0 to 2.4 µg/mL and MIC values were evaluated after 24 h incubation at 37 °C. Subsequently, MTT assay was used to estimate anti-proliferative activity of these methanol extracts and of F. bubu latex on three human cancer cell lines (U373 glioblastoma, A549 NSCLC, and SKMEL-28 melanoma). RESULTS: The methanol extract of F. bubu stem bark exhibited the highest antimicrobial activity against C. albicans with a MIC value of 9.8 µg/mL, while the F. bubu latex and the methanol extract of F. bubu leaves induced significant anti-proliferative activity against lung (IC50 values of 10 and 14 µg/mL, respectively) and glioma (IC50 values of 13 and 16 µg/mL, respectively) cancer cells. CONCLUSION: These results indicate that effective drugs could be derived from the three studied plants.

Chemical constituents from Glyphaea brevis and Monodora myristica: chemotaxonomic significance.

A chemical investigation of the Glyphaea brevis leaves and of the Monodora myristica fruits led to the identification of thirteen compounds, seven linear long-chain aliphatic compounds, 1, 2, 4, 6, and 9-11, three steroids, 3a, 3b, and 7, two triterpenes, 5a and 5b, and one polyol, 8. The compounds 2 and 8, previously mentioned in the literature, are here characterized by their complete (1)H- and (13)C-NMR assignments. This is the first report of a full NMR assignment for linear fatty acid esters of aliphatic primary alcohols and for meso-erythritol. Compound 5b and 8 were isolated for the first time from plant extracts of the Tiliaceae family, and compounds 9-11 from the Annonaceae plant family. Our results constitute the basis for further chemotaxonomic studies on the two species.

In vitro sensitivity of Plasmodium falciparum field isolates to extracts from Cameroonian Annonaceae plants.

In a search for new plant-derived antimalarial extracts, 19 fractions were obtained from three Annonaceae species, Uvariopsis congolana (leaf, stem), Polyalthia oliveri (stem bark), and Enantia chlorantha (stem, stem bark) with yields ranging from 0.33% to 4.60%. The extracts were prepared from 500 g of each plant part, using organic solvents to afford five methanolic fractions (acetogenin rich), five water fractions, five hexane fractions, and four interface precipitates. Evaluation of the activity of fractions in vitro against field isolates of the malaria parasite Plasmodium falciparum showed that acetogenin-rich fractions and interface precipitates were the most potent, with IC(50) values ranging from 0.05 to 8.09 µg/ml. Sensitivity of parasite isolates to plant extracts varied greatly, with over 100-fold difference from isolate to isolate in some cases. The active acetogenin-rich fractions and interface precipitates were assessed in combination with chloroquine in the same conditions, and showed additive interaction in the huge majority of cases. Synergistic interactions were found in some cases with acetogenin-rich fractions. Acute toxicity of promising fractions was evaluated through oral administration in Swiss albino mice. Tested fractions appeared to be safe, with LD(50) values higher than 2 g/kg. In summary, acetogenin-rich fractions from Annonaceae species showed high potency against P. falciparum field isolates and safety by oral administration in mice, supporting their detailed investigation for antimalarial drug discovery.

Bioguided isolation of antiplasmodial secondary metabolites from Persea americana Mill. (Lauraceae).

The antiplasmodium assay-guided investigation of the roots, stem bark, and leaves of Persea americana Mill. led to the isolation of a new fatty alcohol, perseatriol (1), along with six known compounds (2-7). Their structures were elucidated based on the analysis of their NMR and MS data. All crude extracts and fractions exhibited good antiplasmodial activity on Plasmoduim falciparum 3D7 with IC50 values ranging from 0.76 to 10.5 µg/mL; they also displayed cytotoxicity against HeLa cells with low selectivity indexes (SIs). A preliminary Plasmodium lactate dehydrogenase (pLDH) assay was also performed on the isolated compounds. 9,9'-Di-O-feruloyl-5,5'-dimethoxysecoisolariciresinol (4) turned out to be non-toxic and displayed the best activities on P. falciparum with an IC50 value of 0.05 µM, comparable to the reference drug chloroquine with an IC50 value of 0.03 µM. Furthermore, besides compound 4, this work reports the first isolation of lutein (2) and scopoletin (3) from P. americana. The crude extracts of roots, stem bark, and leaves of P. americana, their fractions and compounds completely suppressed the growth of P. falciparum. The observed activity supports the use of P. americana in folk medicine for the treatment of malaria.

Isoflavone dimers and other bioactive constituents from the figs of Ficus mucuso.

Phytochemical investigation of the figs of Ficus mucuso led to the isolation of three new isoflavone dimer derivatives, mucusisoflavones A-C (1-3), together with 16 known compounds. Some of the isolates were tested in vitro for their inhibitory properties toward ß-glucuronidase and Plasmodium falciparum enoyl-ACP reductase (PfENR) enzymes. Compound 1 (IC50) 0.68 µM) showed inhibitory activity on ß-glucuronidase enzyme, while 3 (IC50) 7.69 µM) exhibited a weak inhibitory activity against P. falciparum enoyl-ACP reductase (PfENR).

Antiplasmodial constituents from the fruit pericarp of Pentadesma butyracea.

Bioassay-guided fractionation of the fruit pericarp of Pentadesma butyracea, using the antiplasmodial test, led to the isolation of a new xanthone, named pentadexanthone (1), together with six known compounds: cratoxylone (2), α-mangostin (3), 1,3,5-trihydroxy-2-methoxyxanthone (4), garcinone E (5), (-)-epicathechin (6), and lupeol (7). The structure of 1 was elucidated by spectroscopic data analysis. An antiplasmodial assay was performed with the isolates, in which compounds 1- 3 and 5 exhibited potent activity in vitro against Plasmodium falciparum chloroquine-resistant strain W2, with IC50 values below 3 µM.

Antifeedant and ovicidal activities of a new cassane and other compounds from Caesalpinia welwitschiana Oliv. and Caesalpinia bonduc L. against Tuta absoluta (Lepidoptera: Gelechiidae).

Methanolic extracts of liana of Caesalpinia welwitschiana and leaves of C. bonduc were found to possess moderate antifeedant and ovicidal activities against Tuta absoluta. Bioassay-guided isolation of constituents from the most active fraction of C. welwitschiana led to the identification of four known compounds [isobonducellin 1a and bonducellin 1 b, intricatinol 2, (-)-epigallocatechin-3-O-gallate 4] and one new constituent [welwitschianic acid 3]. The most active fraction of C. bonduc afforded two known constituents neocaesalpin L 5 and neocaesalpin A 6. The isolated structures were elucidated on the basis of their MS, UV, IR and 1 & 2 D NMR spectra and by comparison with literature data. Compounds 2, 4-6 were showed antifeedant and ovicidal properties against T. absoluta, some comparable to that of azadirachtin at 50, 100 and 200 ng/µl. Overall, the present study, conclude that the two species of the plant could be a promising source of eco-friendly botanical constituents.

Ceramide and Cerebroside from the stem bark of Ficus mucuso (Moraceae).

Two new sphingolipids mucusamide (1) and mucusoside (2) have been isolated from methanol soluble part of the stem bark of Ficus mucuso WELW., together with fifteen known secondary metabolites including cellobiosylsterol (3), ß-sitosterol (4), stigmasterol (5), ß-sitosterol 3-O-ß-D-glucopyranoside (6), lupeol acetate (7), ursolic acid (8), procatechuic acid (9), 2-methyl-5,7-dihydroxychromone 8-C-ß-D-glucoside (10), apigenin (11), (-)-epicatechin (12), (+)-catechin (13), N-benzoyl-L-phenylalanilol (14), α-acetylamino-phenylpropyl α-benzoylamino-phenylpropionate (15), asperphenamate (16) and bejaminamide (17). Structures of compounds 1 and 2 were elucidated by spectroscopic analysis and chemical methods.

Cytotoxic and antiplasmodial xanthones from Pentadesma butyracea.

Four new xanthones, butyraxanthones A-D (1-4), were isolated from the stem bark of Pentadesma butyracea, together with six known xanthones (5-10) and a triterpenoid (lupeol). The structures of 1-4 were established by spectroscopic methods. Compounds 1-10 were tested in vitro for antiplasmodial activity against a Plasmodium falciparum chloroquine-resistant strain and for cytotoxicity against a human breast cancer cell line (MCF-7). Nearly all of these xanthones exhibited good antiplasmodial activity, and some of them also demonstrated potent cytotoxicity.

Bioactive constituents of the stem bark of Beilschmiedia zenkeri.

Phytochemical investigation of the stem bark of Beilschmiedia zenkeri led to the isolation of four new methoxylated flavonoid derivatives, (2S,4R)-5,6,7-trimethoxyflavan-4-ol (1), (2S,4R)-4,5,6,7-tetramethoxyflavan (2), beilschmieflavonoid A (3), and beilschmieflavonoid B (4), together with seven known compounds. The structures of 1-4 were established by spectroscopic methods, and their relative configurations confirmed by X-ray crystallographic and CD analysis. The isolated compounds were evaluated in vitro for their antibacterial activity against three strains of bacteria, Pseudomonas agarici, Bacillus subtilis, and Streptococcus minor, and for their antiplasmodial activity against Plasmodium falciparum, chloroquine-resistant strain W2.

Two new antimicrobial dimeric compounds: febrifuquinone, a vismione-anthraquinone coupled pigment and adamabianthrone, from two Psorospermum species.

Febrifuquinone (1), a new vismione-anthraquinone coupled pigment and a new bianthrone named adamabianthrone (2), were isolated respectively, from the roots of Psorospermum febrifugum and from the bark of Psorospermum adamauense along with eight known compounds including: two bianthrones [(bianthrone A(1) (3) and bianthrone A(2b)], one vismione [(vismione D (4)], one anthrone (3-geranyloxyemodin anthrone) and four anthraquinones [(1,8-dihydroxy-3-isoprenyloxy-6-methylanthraquinone, emodin (5), 3-geranyloxy-1,8-dihydroxy-6-methylanthraquinone and 2-geranyl-1,8-dihydroxy-6-methylanthraquinone]. Their structures were determined using modern spectroscopic methods including one and two dimensional-NMR techniques as well as MS. Compounds 1 and 2 showed significant antimicrobial activities against a wide range of bacteria and fungi.

Antimalarial compounds from the stem bark of Vismia laurentii.

A phytochemical study of the stem bark of Vismia laurentii resulted in the isolation of a tetracyclic triterpene, tirucalla-7,24-dien-3-one (1), and seven other known compounds: 3-geranyloxyemodin (2), vismiaquinone A (3), vismiaquinone B (4), bivismiaquinone (5), epifriedelinol (6), betulinic acid (7) and stigmasta-7,22-dien-3-ol (8). The structure of all these compounds was elucidated by spectroscopic means. The stem bark extract and compounds 1 and 3 showed good antimalarial activity against the W2 strain of Plasmodium falciparum.

Anthraquinones from the fruits of Vismia laurentii.

Phytochemical study of the fruits of Vismia laurentii resulted in the isolation of five structurally related compounds. Three of them are constituents, namely, laurentiquinone A (1) (methyl 1,6,8-trihydroxy-3-methyl-7-(3-methylbut-2-enyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate), laurentiquinone B (2) (methyl 5,7-dihydroxy-2,2,9-trimethyl-6,11-dioxo-6,11-dihydro-2H-anthra[2,3-b]pyran-8-carboxylate) and laurentiquinone C (3) (methyl 9-(ethanoyloxymethyl)-5,7-dihydroxy-2,2-dimethyl-6,11-dioxo-6,11-dihydro-2H-anthra[2,3-b]pyran-8-carboxylate) and two are known compounds, emodin (4) and isoxanthorin (5). Their structures were elucidated by spectroscopic means. Crude extracts of hexane and EtOAc showed anti-plasmodial activity against the W2 strain of Plasmodium falciparum.

Bioactive aristolactams from Piper umbellatum.

Four alkaloids named piperumbellactams A-D (1-4) were isolated from branches of Piper umbellatum together with known N-hydroxyaristolam II (5), N-p-coumaroyl tyramine (6), 4-nerolidylcatechol (7), N-trans-feruloyltyramine, E-3-(3,4-dihydroxyphenyl)-N-2-[4-hydroxyphenylethyl]-2-propenamide, beta-amyrin, friedelin, apigenin 8-C-neohesperidoside, acacetin 6-C-beta-d-glucopyranoside, beta-sitosterol, its 3-O-beta-d-glucopyranoside and its 3-O-beta-d-[6'-dodecanoyl]-glucopyranoside. Glycosidase inhibition, antioxidant and antifungal activities of these compounds were evaluated. Compounds 1-3 showed moderate alpha-glucosidase enzyme inhibition with IC50 values 98.07+/-0.44, 43.80+/-0.56 and 29.64+/-0.46, respectively. In DPPH radical scavenging assay, compounds 2, 3 and 6 showed potent inhibitory activity while compounds 4, 5 and 7 showed potent antifungal activity.

Spathoside, a cerebroside and other antibacterial constituents of the stem bark of Spathodea campanulata.

Spathoside, a new cerebroside was isolated from the stem bark of Spathodea campanulata, besides known compounds (n-alkanes, linear aliphatic alcohols, sitosterol and their esters, beta-sitosterol-3-O-beta-D-glucopyranoside, oleanolic acid, pomolic acid, p-hydroxybenzoic acid and phenylethanol esters). The structures of the isolated compounds were established by spectroscopic studies. The antibacterial activity of the isolated compounds against a wide range of microorganisms was examined. They inhibited significantly the growth of some gram-positive and -negative bacteria.

Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera (Clusiaceae).

There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC50 < 10 μg·mL−1) with three fungi including Paecilomyces lilacinus (IC50 = 0.44 μg·mL−1), Penicillium janthinellum (IC50 = 0.2 μg·mL−1), and Paecilomyces sp. (IC50 = 0.55 μg·mL−1) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing.

Anthraquinones from the stem bark of Stereospermum zenkeri with antimicrobial activity.

Two anthraquinones, zenkequinones A and B were isolated from the stem bark of Stereospermum zenkeri together with known sterequinone-F, p-coumaric acid, sitosterol-3-O-beta-D-glucopyranoside and 3beta-hydroxyolean-12-en-28-O-beta-D-glucopyranoside. Their structures were established by spectroscopic methods. The antimicrobial activity of the isolated compounds was evaluated against six multiresistant strains of pathogens. Zenkequinone B showed the best antibacterial activity (MIC 9.50 microg/ml) against gram-negative Pseudomonas aeruginosa.

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera.

In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1) and F (4) showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 microM and 0.16 microM, respectively) comparable to that of the reference compound, miltefosine (0.46 microM). Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE) and butylcholinesterase (AChE). For AChE, the IC50 value (0.66 microM) of garcinol (2) was almost equal to that of the reference compound galanthamine (0.50 microM). Furthermore, guttiferone A (1) and guttiferone F (4) (IC50 = 2.77 and 3.50 microM, respectively) were more active than galanthamine (IC50 = 8.5) against BChE.

Compounds from Terminalia mantaly L. (Combretaceae) Stem Bark Exhibit Potent Inhibition against Some Pathogenic Yeasts and Enzymes of Metabolic Significance.

Background: Pathogenic yeasts resistance to current drugs emphasizes the need for new, safe, and cost-effective drugs. Also, new inhibitors are needed to control the effects of enzymes that are implicated in metabolic dysfunctions such as cancer, obesity, and epilepsy. Methods: The anti-yeast extract from Terminalia mantaly (Combretaceae) was fractionated and the structures of the isolated compounds established by means of spectroscopic analysis and comparison with literature data. Activity was assessed against Candida albicans, C. parapsilosis and C. krusei using the microdilution method, and against four enzymes of metabolic significance: glucose-6-phosphate dehydrogenase, human erythrocyte carbonic anhydrase I and II, and glutathione S-transferase. Results: Seven compounds, 3,3'-di-O-methylellagic acid 4'-O-α-rhamnopyranoside; 3-O-methylellagic acid; arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid; arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside; 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid; stigmasterol; and stigmasterol 3-O-ß-d-glucopyranoside were isolated from the extract. Among those, 3,3'-di-O-methylellagic acid 4'-O-α-rhamnopyranoside, 3-O-methylellagic acid, and arjunglucoside showed anti-yeast activity comparable to that of reference fluconazole with minimal inhibitory concentrations (MIC) below 32 µg/mL. Besides, Arjunglucoside potently inhibited the tested enzymes with 50% inhibitory concentrations (IC50) below 4 µM and inhibitory constant (Ki) <3 µM. Conclusions: The results achieved indicate that further SAR studies will likely identify potent hit derivatives that should subsequently enter the drug development pipeline.