Evaluation of anti-quorum sensing and antibiofilm effects of secondary metabolites from Gambeya lacourtiana (De Wild) Aubr. & Pellegr against selected pathogens.

BACKGROUND: Microbial infections cause serious health problems especially with the rising antibiotic resistance which accounts for about 700,000 human deaths annually. Antibiotics which target bacterial death encounter microbial resistance with time, hence, there is an urgent need for the search of antimicrobial substances which target disruption of virulence factors such as biofilm and quorum sensing (QS) with selective pressure on the pathogens so as to avoid resistance. METHODS: Natural products are suitable leads for antimicrobial drugs that can inhibit bacterial biofilms and QS. Twenty compounds isolated from the medicinal plant Gambeya lacourtiana were evaluated for their antibiofilm and anti-quorum sensing effects against selected pathogenic bacteria. RESULTS: Most of the compounds inhibited violacein production in Chromobacterium violaceum CV12472 and the most active compound, Epicatechin had 100% inhibition at MIC (Minimal Inhibitory Concentration) and was the only compound to inhibit violacein production at MIC/8 with percentage inhibition of 17.2 ± 0.9%. Since the bacteria C. violaceum produces violacein while growing, the inhibition of the production of this pigment reflects the inhibition of signal production. Equally, some compounds inhibited violacein production by C. violaceum CV026 in the midst of an externally supplied acylhomoserine lactone, indicating that they disrupted signal molecule reception. Most of the compounds exhibited biofilm inhibition on Staphyloccocus aureus, Escherichia coli and Candida albicans and it was observed that the Gram-positive bacteria biofilm was most susceptible. The triterpenoids bearing carboxylic acid group, the ceramide and epicatechin were the most active compounds compared to others. CONCLUSION: Since some of the compounds disrupted QS mediated processes in bacteria, it indicates that this plant is a source of antibiotics drugs that can reduce microbial resistance.

Polyoxygenated Stigmastane-Type Steroids from Vernonia kotschyana Sch. Bip. ex Walp. and Their Chemophenetic Significance.

Four polyoxygenated stigmastanes (1-4) alongside known analogues (7-8) and flavonoids (5-6) were isolated from a dichloromethane/methanol (1:1, v/v) extract of the whole plant of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae). Their structures were determined by means of spectroscopic and spectrometric analysis. The relative stereochemistry of the new compounds was established and confirmed via biosynthesis evidence and cyclization of 1 under acidic conditions. A plausible biosynthetic pathway to the new compounds and the chemophenetic significance of the isolated constituents were also discussed. The crude extract, fractions, and compounds (1-3) were assessed for their antibacterial activity against five highly prevalent bacterial strains. The fractions and compounds showed low to moderate activity with minimal inhibitory concentrations (MICs) > 125 µg/mL.

In vitro antiplasmodial activity and toxicological profile of extracts, fractions and chemical constituents of leaves and stem bark from Dacryodes edulis (Burseraceae).

BACKGROUND: Dacryodes edulis is a plant that belongs to the Burseraceae family. It is widely used traditionally alone or in association with other plants in Cameroonian folk medicine to cure wounds, fever, headaches, and malaria. The aim of this work was to investigate the leaves and stem bark of D. edulis with an emphasis on the antiplasmodial and cytotoxic effects of extracts, fractions, and isolated compounds. METHODS: Extracts, fractions, and some isolated compounds were subjected to antiplasmodial activity screening in vitro against chloroquine-sensitive 3D7 and multidrug resistant Dd2 strains of Plasmodium falciparum using a SyBr Green fluorescence-based assay. The cytotoxicity of active extracts, fractions, and compounds was tested against mammalian Raw cell lines using an in vitro resazurin-based viability assay. The structures of the compounds were determined based on their NMR and MS data. The in vivo toxicity using female BALB/c mice was performed on the most active extract according to the protocol of OECD (2002), guideline 423. RESULTS: The hydroethanolic extract from the leaves of D. edulis displayed good antiplasmodial activity with IC50 values of 3.10 and 3.56 µg/mL respectively on sensitive (3D7) and multiresistant (Dd2) strains of P. falciparum. Of the sixteen compounds isolated, 3,3',4-tri-O-methylellagic acid (4) exhibited the highest antiplasmodial activity against PfDd2 strains with an IC50 value of 0.63 µg/mL. All extracts, fractions, and isolated compounds demonstrated no cytotoxicity against Raw cell lines with CC50 > 250 µg/mL. In addition, the most active extract on both strains of P. falciparum was nontoxic in vivo, with a LD50 greater than 2000 and 5000 mg/kg. A phytochemical investigation of the stem bark and leaves of D. edulis afforded sixteen compounds, including two xanthones (1-2), three ellagic acid derivatives (3-5), one phenolic compound (6), one depside (7), one triglyceride (8), one auranthiamide acetate (9), one gallic acid derivative (10), four triterpenoids (11-14), and two steroids (15-16). Compounds 1, 2, 5, 7, 8, and 9 were herein reported for the first time from the Burseraceae family. CONCLUSION: This work highlights the good in vitro antiplasmodial potency of the hydroethanolic extract of the leaves of this plant and that of two isolated constituents (3,3',4-tri-O-methylellagic acid and ethylgallate) from the plant. These biological results support the use of D. edulis in traditional medicine against malaria.

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.

Elemane-Type Sesquiterpene, Acetonide Derived Polyacetylene and Other Constituents from the Whole Plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. and Their Chemophenetic Significance.

The chemical investigation of the methanol extract of the whole plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. (Asteraceae) led to the isolation of a new elemane-type sesquiterpene (1), a new acetonide derived polyacetylene (2) and a naturally occurring compound (3) from the plant kingdom along with sixteen known compounds (4-19). Their structures were elucidated by extensive NMR and MS analysis. This is the first report on the chemical constituents of G. theophrastifolium. Furthermore, compounds 12, 13, and 14 are reported for the first time from the family Asteraceae, while compound 9 is reported for the first time from the genus Gymnanthemum. Thus, the present results provide valuable insights to the chemophenetic knowledge of G. theophrastifolium, which is also discussed in this work.

Constituents of the Stem Bark of Symphonia globulifera Linn. f. with Antileishmanial and Antibacterial Activities.

The chemical investigation of the n-hexane fraction from the methanol extract of the stem bark of Symphonia globulifera Linn f., which displayed good in vitro activity against Leishmania donovani NR-48822 promastigotes (IC50 43.11 µg/mL), led to the isolation of three previously unreported polyprenylated benzophenones, guttiferone U (1), V (2)/W (3), and a new tocotrienol derivative named globuliferanol (4), along with 11 known compounds (5-15). Their structures were elucidated based on their NMR and MS data. Some isolated compounds were assessed for both their antileishmanial and cytotoxic activities against L. donovani and Vero cells, respectively. Guttiferone K (5) exhibited the best potency (IC50 3.30 µg/mL), but with low selectivity to Vero cells. The n-hexane fraction and some compounds were also assessed in vitro for their antibacterial activity against seven bacterial strains. All the samples exhibited moderate to potent antibacterial activity (MICs ≤ 15.6 µg/mL) against at least one of the tested strains.

Bioactive constituents from Flacourtia vogelii Hook.f. (Flacourtiaceae).

The chemical investigation of the methanolic root extract of Flacourtia vogelii led to the isolation of a new arylbenzoate derivative, vogelinal (1), together with thirteen known compounds (2-14). The structures of the isolates were elucidated by extensive spectroscopic and spectrometric analyses (1D and 2D NMR, ESI-MS) and by comparison with previously reported data. All the compounds were tested for their antioxidant, antifungal and antibacterial activities. Compound 7 exhibited the highest antioxidant potential, with RSa50of 11.80 ± 2.13 µg/mL, RSa50of 42.60 ± 6.32 µg/mL and RC50 of 51.60 ± 7.71 µg/mL for the DPPH, ABTS and FRAP assay, respectively. Compound 13 displayed weak antifungal effect with MIC value of 125 µg/mL against Candida parapsilosis. Compound 8 showed weak antibacterial effect with MIC value of 125 µg/mL, against Shigella dysenteria. The present study, conclude that this species could be a promising source of antioxidant and antibacterial constituents.

Coumarinolignoid and Indole Alkaloids from the Roots of the Hybrid Plant Citrus × paradisi Macfad (Rutaceae).

A phytochemical investigation of the roots of Citrus × paradisi Macfad. (Rutaceae) led to the isolation of two new compounds, namely 1-formyl-5-hydroxy-N-methylindolin-1-ium (1) and decyloxycleomiscosin D (2), along with ten known compounds: 1,1-dimethylpyrrolidin-1-ium-2-carboxylate (3), furan-2,3-diol (4), 5-methoxyseselin (5), umbelliferone (6), scopoletin (7), citracridone I (8), citracridone II (9), citracridone III (10), limonin (11) and lupeol (12). The structures were determined through the comprehensive spectroscopic analysis of 1D and 2D NMR and EI- and ESI-MS, as well as a comparison with the published data. Notably, compounds 3 and 4 from the genus Citrus are reported here for the first time. In addition, the MeOH extract of the roots and compounds 1-7 were screened against the human adenocarcinoma alveolar basal epithelial cell line A549 and the Caucasian prostate adenocarcinoma cell line PC3 using the MTT assay. While the extract showed significant activity, with IC50 values of 35.2 and 38.1 µg/mL, respectively, compounds 1-7 showed weak activity, with IC50 values of 99.2 to 250.2 µM and 99.5 to 192.7 µM, respectively.

Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines.

BACKGROUND: Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples. METHODS: Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry. RESULTS: Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53-/- colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53+/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels. CONCLUSION: BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.

Curative anti-typhoid effect of Detarium microcarpum Guill. & Perr. (Leguminosae) hydroethanolic extract root bark based-on in vivo and molecular docking analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Detarium microcarpum is used to treat typhoid fever, a major public health problem, by indigenous population in Africa. Though its preventive activities have been documented, the curative effect is still to be confirmed. AIM OF THE STUDY: This study aimed at evaluating the curative effects of the hydroethanolic extract of Detarium microcarpum root bark on Salmonella typhimurium-induced typhoid in rat and exploring the in-silico inhibition of some bacterial key enzymes. STUDY DESIGN: In vitro antioxydant, in vivo antisalmonella of the extract and in silico molecular docking assay on the isolated compounds were carried out to explore the anti-salmonella effects of Detarium microcarpum. MATERIAL AND METHODS: The in vitro antioxidant properties of the extract were evaluated using DPPH, ABTS and FRAP tests. The anti-salmonella activity of the extract was assessed through feacal sample from Salmonella typhimurium-infected rat cultured in Salmonella-Shigella agar (SS agar) medium. The affinity of isolated compounds (Rhinocerotinoic acid and Microcarposide) from the extract were performed on four key enzymes (Adenylosuccinate lyase, Acetyl coenzyme A synthetase, Thymidine phosphorylase and LuxS-Quorum sensor) using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: Crude extract of D. microcarpum root bark showed variable activities on DPPH (RSa50: 6.09 ± 1.04 µg/mL), ABTS (RSa50: 24.46 ± 0.27), and FRAP (RSa50: 23.30 ± 0.23). The extract at all the doses exhibited significant healing effect of infected rats, with the complete clearance. The extract restored hematological, biochemical and histological parameters closed to the normal control. The molecular docking results indicates that rhinocerotinoic acid and microcarposide present more affinity to the LuxS-Quorum sensor and Acetyl coenzyme A synthetase protein as compared to the others. CONCLUSION: These results demonstrate potent anti-typhoid activities of the hydroethanolic of Detarium microcarpum root bark extract through antioxidant properties and high inhibitory affinity of its compounds on some bacterial key enzymes that justify its use as traditional medicine to typhoid fever.

Antibacterial constituents of Rumex nepalensis spreng and its emodin derivatives.

The CH2Cl2-MeOH (1:1) extract of roots of Rumex nepalensis (Polygonaceae) displayed significant antibacterial activity against five bacterial strains with MICs (62.5-31.2 µg.mL-1). The EtOAc soluble fraction displayed a significant activity against the same strains with MICs (31.2-3.9 µg.mL-1). The purification of the EtOAc fraction yielded one new phenylisobenzofuranone derivative, berquaertiide (1), along with 19 known compounds (2-20). Their structures were elucidated based on the analysis of their NMR and MS data. All the isolated compounds were assessed for their antibacterial activity. Compound 2 was the most active against all the tested strains (15.7 to 1.9 µg.mL-1), while compounds 3-7 displayed good activities on at least one of the tested strains. In addition, seven analogues (21-27) of compound 2 were prepared and further assessed for their antibacterial activity. Compounds 26 and 27 were most active than 2 against Salmonella enterica and Klebsiella pneumoniae with MIC (125 and 15.6 µg.mL-1, respectively).

One new constituent from the stem bark of Chrysophyllum lacourtianum De Wild. (sapotaceae).

The phytochemical investigation of the methanol extract of the stem bark of Chrysophyllum lacourtianum led to the isolation and characterization of one new secondary metabolite, lacourtianal (1), together with eight known compounds. Compounds 2; 3; 5; 6; 7 and 9 were reported for the first time from Chrysophyllum genus. The structures of compounds 1-9 were elucidated on the basis of 1 D and 2 D NMR spectroscopic and mass spectrometric data as well as comparison with the literature. The antibacterial activity of the methanol extract, fractions and compounds 1-9 were evaluated against bacterial strains. The methanol extract exhibited moderate activity against Staphylococcus aureus NR4674 with MIC values of 500 µg/mL. The n-hexane fraction showed moderate activity against Staphylococcus aureus (ATCC 43300 and ATCC 25923) with MIC values of 125 µg/mL and ursolic acid (5) exhibited strong activity against Enterobacter aerogenes CPC and Escherichia coli ATCC 25322 with MIC values of 7.8 and 3.9 µg/mL respectively.

Two new secondary metabolites with antibacterial activities from Conyza aegyptiaca (Asteraceae).

The bio guided fractionation of the dichloromethane/methanol (1:1) crude extract of the air-dried whole plant of C. aegyptiaca led to the isolation of one new flavone derivative designated conyflavone (1) and one new clerodane diterpene type designated conyclerodane (2) along with five known compounds including two flavonoids Gardenin C (3), chrysosplenetin (4) and two steroids glucoside of ß-sitosterol (5), the mixture of stigmasterol (6) and ß-sitosterol (6') and ent-2b,18,19trihydroxycleroda-3,13-dien-16,15-olide (7). The structures were established by spectroscopic methods including IR, 1D and 2D NMR in conjunction with mass spectroscopy and by comparison to data of related compounds described in literature. The stereocentres in compound 2 were determined by SC-XRD analysis. Crude extract as well as fractions and pure compounds were evaluated in vitro for their antibacterial activities against four pathogenic and two clinical isolate strains using microdilution methods. Extracts and compounds displayed a moderate antibacterial activity with MIC values ranging from 125 to 500 µg/mL.

Bioactive Arylnaphthalide Lignans from Justicia depauperata.

Eleven previously undescribed arylnaphthalide lignans (1-11) together with seven known compounds were isolated from the whole plant of Justicia depauperata. The structures of 1-11 were elucidated by spectroscopic analysis and mass spectrometry. Compounds 6 (IC50 = 4.1 µM) and 9 (IC50 = 9.5 µM) displayed cytotoxic activity against the KB-3-1 cervical carcinoma cell line. This report provides an insight into the conformational equilibria occurring in the arylnaphthalide lignan constituents of this plant.

Chemical Constituents of Macaranga occidentalis, Antimicrobial and Chemophenetic Studies.

Medicinal plants are known as sources of potential antimicrobial compounds belonging to different classes. The aim of the present work was to evaluate the antimicrobial potential of the crude extract, fractions, and some isolated secondary metabolites from the leaves of Macaranga occidentalis, a Cameroonian medicinal plant traditionally used for the treatment of microbial infections. Repeated column chromatography of the ethyl acetate and n-butanol fractions led to the isolation of seventeen previously known compounds (1-17), among which three steroids (1-3), one triterpene (4), four flavonoids (5-8), two stilbenoids (9 and 10) four ellagic acid derivatives (11-14), one geraniinic acid derivative (15), one coumarine (16), and one glyceride (17). Their structures were elucidated mainly by means of extensive spectroscopic and spectrometric (1D and 2D NMR and, MS) analysis and comparison with the published data. The crude extract, fractions, and isolated compounds were all screened for their antimicrobial activity. None of the natural compounds was active against Candida strains. However, the crude extract, fractions, and compounds showed varying levels of antibacterial properties against at least one of the tested bacterial strains, with minimal inhibitory concentrations (MICs) ranging from 250 to 1000 µg/mL. The n-butanol (n-BuOH) fraction was the most active against Escherichia coli ATCC 25922, with an MIC value of 250 µg/mL. Among the isolated compounds, schweinfurthin B (10) exhibited the best activity against Staphylococcus aureus NR 46003 with a MIC value of 62.5 µg/mL. In addition, schweinfurthin O (9) and isomacarangin (6) also exhibited moderate activity against the same strain with a MIC value of 125 µg/mL. Therefore, pharmacomodulation was performed on compound 6 and three new semisynthetic derivatives (6a-c) were prepared by allylation and acetylation reactions and screened for their in vitro antimicrobial activity. None of the semisynthetic derivatives showed antimicrobial activity against the same tested strains. The chemophenetic significance of the isolated compounds is also discussed in this paper.

Two new flavone glycosides from the leaves of Ochna afzelii Oliv. (Ochnaceae).

Two new glycosylflavones, 6''-O-acetyl-8-C-ß-D-galactopyranosylchrysoeriol (1) and 8-C-ß-D-galactopyranosylchrysoeriol (2) were isolated from the methanol extract of the leaves of Ochna afzelii Oliv., along with four known compounds namely 8-C-ß-D-galactopyranosylapigenin (3), ochnaflavone (4), sitosterol-3-O-ß-D-glucopyranoside (5) and D-mannitol (6). Isolation was performed chromatographically and the structures of the purified compounds were elucidated by analyzing their spectroscopic and mass spectrometric data. The antibacterial activity of extract, fractions, and compounds 1 - 4 was evaluated using broth microdilution method against Gram-positive and Gram-negative bacteria while the antioxidant capacity was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the ferric reducing antioxidant power (FRAP) methods. The new flavones (1 and 2) displayed moderate antibacterial activities (MIC = 32 - 64 µg/mL) and weak antioxidant properties.

Antimicrobial and Cytotoxic Activities of Constituents from the Fruit of Albizia lebbeck L. Benth (Fabaceae).

Twenty-two compounds were isolated from the fruit of Albizia lebbeck including one unprecedented, rare amino acid-derived zwitterionic and one new flavone derivative. The isolation was performed on repeated column chromatography over silica gel and their structures were determined by 1D-, 2D-NMR and HR-ESI-MS spectra together with reported data in the literature. The chemophenetic significance is also discussed. Some isolated compounds were reported for the first time to be found in the species. Additionally, compound 2 showed antibacterial activity and compounds 1 and 2 revealed moderate cytotoxic activity against the Raw 264.7 cancer cell line with IC50 values of 37.19 µM and 29.36 µM, respectively. Furthermore, a proposed biosynthetic pathway of compound 1 is described.

Chemical Constituents of the Stem Bark of the Hybrid Plant Citrus × paradisi Macfad. (Rutaceae).

The stem bark of Citrus × paradisi Macfad. (Rutaceae) gave (23S)-isolimonexic acid (1), limonin (2), citracridone II (3), citpressine II (4), citpressine I (5), grandisine (6), 2-hydroxynoracronycine (7), citracridone I (8), 5-methoxyseselin (9), umbelliferone (10), scopoletin (11), naringenin (12), apigenin (13), friedelin (14), agrostophyllinone (15) and stigmasterol-3-O-ß-D-glucopyranoside (16). The structures of the compounds were determined using NMR and MS spectroscopic data, and by comparison with published data. The relative configuration of 1 was proposed as (23S)-isolimonexic acid using NOE studies. Hydrogenation reaction of compound 3 led to the new derivative 3',4'-dihydrocitracridone II (3a). Cytotoxicity activities against the human adenocarcinoma alveolar basal epithelial cell lines A549 and the Caucasian prostate adenocarcinoma cell lines PC3, using the MTT assays showed that the methanol crude extract was significant with IC50 values of 30.1 and 31.7 µg/mL, respectively, with the positive control, doxorubicin giving an IC50 of 0.9 µM. In addition, compounds 3, 7 and 8 gave moderate cytotoxic activities with IC50 values of 33.1, 31.2 and 32.5 µM for A549 cells and 35.7, 33.8 and 34.9 µM for PC3 cells, respectively. The hydrogenated 3a was less active than 3, suggesting that the presence of the double bond in pyrans is important for structure-activity relationship.

Constituents from ripe figs of Ficus vallis-choudae Delile (Moraceae) with antiplasmodial activity.

Ripe figs, barks, and wood of Ficus vallis-choudae are used in traditional medicine against several conditions including nausea and malaria. However, its use is still to be scientifically documented and validated. Hence, the aim of the present work was to evaluate the antiplasmodial activity of the dichloromethane-methanol (DCM-MeOH (1:1)) crude extract, their hexane, dichloromethane, ethyl acetate, and methanoli fractions, as well as the isolated chemical constituents. The chemical study of the DCM-MeOH (1:1) crude extract of F. vallis-choudae figs led to the isolation of fifteen (15) known compounds identified based on their spectroscopic data [one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), mass spectrometry] and by comparison of these data with those reported in the literature. Some of the isolated compounds were assessed in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-sensitive 3D7 (Pf3D7) and multidrug-resistant Dd2 strains. The dichloromethane fraction exhibited very good antiplasmodial activity against both strains with IC50 values of 13.86 µg/mL and 8.18 µg/mL, respectively. Among the tested compounds, wighteone (2) was the most active against P. falciparum 3D7 (IC50 = 24.6 ± 1.5 µM) and Dd2 (IC50 = 11.9 ± 2.4 µM) strains. The obtained results could justify the traditional uses of F. vallis-choudae against malaria. Wighteone appears to be the most active ingredient. However, further consideration of this compound as starting point for antimalarial drug discovery will depend upon its selectivity of action towards Plasmodium parasites. HIGHLIGHTS: • 15 (fifteen) compounds were isolated from the dichloromethane-methanol extract of Ficus vallis-choudae. • Their structures were determined on the basis of their spectroscopic data. • The dichloromethane fraction showed promising activities on the Pf3D7 and PfDd2 strains with IC50 values of 13.86 and 8.18 µg/mL, respectively. • Wighteone was the most active compound against PfDd2 (IC50 = 11.9 ± 2.4 µM).

Secondary metabolites from Detarium microcarpum Guill. and Perr. (Fabaceae).

The chemical investigation of the ethanol/water (7:3) extract of the roots of Detarium microcarpum (Fabaceae) led to the isolation of one new labdane diterpenoid, microcarpin (1) and one new ceramide derivative, microcarpamide (2), along with eight known secondary metabolites (3-10) including, 5-(carboxymethyl)-5,6,8a-trimethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene-1-carboxylic acid (3), microcarposide (4), rhinocerotinoic acid (5), 1,7-dihydroxy-6-methylxanthone (6), ursolic acid (7), 3ß,23-dihydroxylup-20(29)-en-28-oic acid (8), alphitolic acid (9), and stigmasterol glucoside (10). The structures of these compounds were elucidated based on their spectroscopic data. Although compounds 3 and 4 are known, their crystalline structures are reported here for the first time. These compounds were evaluated in vitro for their antisalmonella activity. The results obtained showed that, microcarpamide (2), microcarposide (4), and rhinocerotinoic acid (5) were moderately active against three salmonella strains: Salmonella typhi, Salmonella enteritidis and Salmonella typhimirium, with minimum inhibition concentration values of 76.7 and 153.5 µM.