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).     

Cholinesterase inhibiting and antiplasmodial steroidal alkaloids from Sarcococca hookeriana

Bioguided phytochemical investigation of Sarcococca hookeriana with respect to the cholinesterase enzyme inhibitory assay yielded two new pregnane-type steriodal alkaloids hookerianamide H (1) and hookerianamide I (2), along with three known alkaloids N(a)-methylepipachysamine D (3), sarcovagine C (4) and dictyophlebine (5). Their structures were determined with the aid of extensive spectroscopic analysis. All compounds showed good inhibitory activities against the enzymes acetylcholinesterase (IC(50) 2.9-34.1 microM) and butyrylcholinesterase (IC(50) 0.3-3.6 microM). These compounds also showed moderate antiplasmodial activity (IC(50) 2.4-10.3 microM) against the Plasmodium falciparum chloroquine resistant W2 strain.     

Chemical constituents of the new endophytic fungus Mycosphaerella sp. nov. and their anti-parasitic activity

Chemical investigation of a new endophytic fungus, Mycosphaerella sp. nov. strain F2140, associated with the foliage of the plant Psychotria horizontalis (Rubiaceae) in Panama, resulted in the isolation of cercosporin (1) and a new cercosporin analog (3) as the major components. The structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-6-ethyl-3-hydroxy-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-5-hydroxy-2-methoxy-6-methyl-cyclohex-2-enone (5), and an isomer of 5 (6). To study the influence of the hydroxy groups on the anti-parasitic activity of cercosporin, compound 1 was acetylated to obtain derivative 2. The isolated compounds 1- 6 were tested in vitro to determine their anti-parasitic activity against the causal agents of malaria (Plasmodium falciparum), leishmaniasis (Leishmania donovani), and Chagas disease (Trypanosoma cruzi). Cytotoxicity and potential anticancer activity of these compounds were evaluated using mammalian Vero cells and MCF7 cancer cell lines, respectively. Compounds 1 and 2 displayed high potency against L. donovani (IC50 0.46 and 0.64 microM), T. cruzi (IC50 1.08 and 0.78 microM), P. falciparum (IC50 1.03 and 2.99 microM), and MCF7 cancer cell lines (IC50 4.68 and 3.56 microM). Compounds 3-6 were not active in these assays at a concentration of 10 microg/mL.     

Endodesmiadiol, a friedelane triterpenoid, and other antiplasmodial compounds from Endodesmia calophylloides

From the ethyl acetate extract of the stem bark of Endodesmia calophylloides (Guttiferae), a novel friedelane triterpenoid named endodesmiadiol (1), as well as the known compounds friedelin (2), canophyllol (3), canophyllal (4), cerin (5), morelloflavone (6), volkensiflavone (7), 8-deoxygartanin (8), 3 beta-acetoxyoleanolic acid (9) and 1,8-dihydroxy-3-isoprenyloxy-6-methylxanthone (10) have been isolated. The structures of these compounds were established by spectroscopic analysis, and the relative configuration of endodesmiadiol (1) was confirmed by X-ray diffraction. The antiplasmodial activity of the isolated compounds was evaluated against the W2 strain of Plasmodium falciparum which is resistant to chloroquine and other antimalarial drugs. All the compounds were found to be active with IC50 values ranging from 7.2 to 23.6 microM. The IC50 of endodesmiadiol was found to be 11.8 microM.     

Prenylated anthraquinones and other constituents from the seeds of Vismia laurentii

Two new prenylated anthraquinones, laurenquinone A (1) and B (2) were isolated from the seeds of Vismia laurentii together with four known compounds; xanthone V(1) (3), physcion (4), 3-geranyloxyemodin anthrone (5) and friedelin (6). The structures of the new metabolites were determined with the help of spectroscopic data including extensive 2D-NMR spectroscopy. The known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. Compounds 1, 4 and 5 exhibited moderate algicidal activity against Chlorella fusca and 3 showed moderate activity against the gram-positive bacterium Bacillus megaterium.     

Synthesis and antiplasmodial activity of 3-furyl and 3-thienylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives

The aim of this study was to identify new compounds active against Plasmodium falciparum based on our previous research carried out on 3-phenyl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds were synthesized and evaluated for antimalarial activity. Eight of them showed an IC(50) less than 1 microM against the 3D7 strain. Derivative 1 demonstrated high potency (IC(50)= 0.63 microM) and good selectivity (SI=10.35), thereby becoming a new lead-compound.     

Antiparasitic and antimicrobial isoflavanquinones from Abrus schimperi

The EtOH extract of Abrus schimperi (Fabaceae), collected in Kenya, demonstrated significant activity against Leishmania donovani promastigotes with IC50 value of 3.6 microg/mL. Bioassay-guided fractionation of CHCl3 fraction using Centrifugal Preparative TLC afforded two antiparasitic isoflavanquinones, namely amorphaquinone (1) and pendulone (2). They displayed IC50 values of 0.63 microg/mL and 0.43 microg/mL, respectively, against L. donovani promastigotes. Both the compounds were also evaluated against L. donovani axenic amastigotes and amastigotes in THPI macrophage cultures. In addition, compounds 1 and 2 showed antiplasmodial activity against Plasmodium falciparum D6 and W2 strains, while 2 displayed antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (each IC50 1.44 microg/mL). The 1H and 13C data of 1, not fully assigned previously, were unambiguously assigned using 1D and 2D NMR HMBC and HMQC experiments. In addition, the absolute stereochemistry of the isolated compounds 1 and 2 was revised as C-(3S) based on Circular Dichroism experiments. This appears to be the first report of amorphaquinone (1) and pendulone (2) from the genus Abrus.     

Antiplasmodial and cytotoxic activities of drimane sesquiterpenes from Canella winterana

The hexane extract from the leaves of Canella winterana exhibited strong activity against the chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10) in vitro (IC50 2.53 microg/mL). Bioassay guided fractionation of this extract has led to the isolation of 5 drimane-type sesquiterpenoids: 9-epideoxymuzigadial, 9-deoxymuzigadial, muzigadial, 3-beta-acetoxypolygodial and the newly isolated hemiacetal, named muzigodiol, with IC50-values of 1.01, 2.19, 0.31, 2.77 and 7.43 microg/mL, respectively. The first four compounds were tested for their cytotoxicity using Chinese Hamster Ovarian (CHO) cells, where they showed IC50-values of 1.82, 33.69, 1.18, and 58.31 microg/mL, respectively. A structure-activity relationship is discussed.     

Antimalarial activity of sesquiterpene lactones from Vernonia cinerea

Two new sesquiterpene lactones, vernolides C and D as well as six known ones were isolated from the dichloromethane fraction of an aqueous extract from Vernonia cinerea. Their structures were elucidated by spectroscopic methods. Among the known sesquiterpene lactones, three of them were described in this plant for the first time. In vitro antiplasmodial evaluation showed that the three major compounds 1, 7 and 8 were active against chloroquine resistant Plasmodium falciparum strain (W2) with IC(50) 3.9, 3.7 and 3.5 microM, respectively.     

Chemical and bioactivity evaluation of the bark of Neonauclea purpurea

Bioassay-guided fractionation of the MeOH extract from the stem bark of Neonauclea purpurea used in traditional medicine, resulted in the isolation of 2 indole alkaloids, cadambine (1) and alpha-dihydrocadambine (2), as well as a quinolic compound, 2,6-dimethoxy-1,4-benzoquinone (3). Antimalarial activity evaluation showed that compounds 2 and 3 exhibited mild in vitro antimalarial activity against Plasmodium falciparum, the chloroquine-resistant strain K1 with IC50 values of 6.6 and 11.3 microM, respectively. Compounds 1 and 2 showed no cytotoxicity to monkey (Vero) cells, but compound 3 showed weak cytotoxicity with an IC50 value of 1.19 microM.     

Ceanothane- and lupane-type triterpenes with antiplasmodial and antimycobacterial activities from Ziziphus cambodiana

One new and eight known ceanothane- and lupane-type triterpenes were isolated from the root bark of Ziziphus cambodiana PIERRE (Rhamnaceae). Based on spectral analyses, the structure of the new compound was elucidated as 3-O-(4-hydroxy-3-methoxybenzoyl)ceanothic acid (3-O-vanillylceanothic acid) (1), while the known compounds were identified as lupeol (2), betulinaldehyde (3), betulinic acid (4), 2-O-E-p-coumaroyl alphitolic acid (5), alphitolic acid (6), zizyberanalic acid (7), zizyberenalic acid (8) and ceanothic acid (9). Compounds 1, 5 and 8 exhibited significant in vitro antiplasmodial activity against the parasite Plasmodium falciparum, with inhibitory concentration (IC50) values of 3.7, 0.9 and 3.0 microg/ml, respectively. Compounds 1 and 3-8 showed antimycobacterial activity against Mycobacterium tuberculosis with respective MIC values of 25, 25, 25, 12.5, 50, 50 and 100 microg/ml.     

Corylucinine, a new alkaloid from Corydalis cava (Fumariaceae), and its cholinesterase activity

A new benzyldihydroisoquinoline alkaloid (1) was isolated from the tubers of Corydalis cava and named corylucinine. Additionally, 8-trichloromethyl-7,8-dihydropalmatine (2), an isolation artifact of tetrahydropalmatine, was obtained. The structures were established by spectroscopic (including 2D NMR and optical rotation) and HR-ESI-MS methods. Both compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. In comparison with the used standards, both compounds showed only moderate inhibitory activity against HuAChE (IC50,. HuAChE = 127.6 +/- 5.2 microM for 1, and IC50, HuAChE = 82.9 +/- 3.9 microM for 2) and none against HuBuChE.     

Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Chelidonium majus (Papaveraceae)

The roots and aerial parts of Chelidonium majus L. were extracted with EtOH and fractionated using CHCl3 and EtOH. Repeated column chromatography, preparative TLC and crystallization led to the isolation of five isoquinoline alkaloids, stylopine (3), chelidonine (4), homochelidonine (5), protopine (6), and allocryptopine (7), along with two isolation artifacts 6-ethoxydihydrosanguinarine (1) and 6-ethoxydihydrochelerythrine (2). All isolated compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. The isolation artifacts exhibited the highest activity against HuAChE and HuBuChE with IC50 values of 0.83 +/- 0.04 microM and 4.20 +/- 0.19 microM for 6-ethoxydihydrochelerythrine and 3.25 +/- 0.24 microM and 4.51 +/- 0.31 microM for 6-ethoxydihydrosanguinarine. The most active of the naturally-occurring alkaloids was chelidonine, which inhibited both HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 26.8 +/- 1.2 microM and 31.9 +/- 1.4 microM, respectively.     

Bioactive constituents of the root bark of Artocarpus rigidus subsp. rigidus

Investigation of the chemical constituents of the root bark of Artocarpus rigidus BLUME subsp. rigidus has led to the isolation of six, structurally diverse phenolic compounds. These included two new compounds with modified skeletons, the flavonoid 7-demethylartonol E (1) and the chromone artorigidusin (2), together with four known phenolic compounds, the xanthone artonol B (3), the flavonoid artonin F (4), the flavonoid cycloartobiloxanthone (5), and the xanthone artoindonesianin C (6). Compounds 1, 4, and 5 exhibited antiplasmodial activity against Plasmodium falciparum. All compounds showed antimycobacterial activity against Mycobacterium tuberculosis, with 4 being the most active compound (MIC 6.25 microg/ml). Compounds 5 and 6 were active against KB cells, whereas 2, 5, and 6 showed varying toxicity to BC cells. Compounds 1-3, 5, and 6 were active in the NCI-H187 cytotoxicity assay, with 3 being the most active compound (IC(50) 1.26 microg/ml).     

Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava (Fumariaceae)

Tubers of Corydalis cava were extracted with ethanol and fractionated using n-hexane, chloroform and ethanol. Repeated column chromatography, preparative TLC and crystallization led to the isolation of fifteen isoquinoline alkaloids. The chemical structures of the isolated compounds were determined on the basis of spectroscopic techniques and by comparison with literature data. All isolated compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. (+)-Canadaline inhibited acetylcholinesterase as well as butyrylcholinesterase in a dose-dependent manner with IC50 values of 20.1 +/- 1.1 microM and 85.2 +/- 3.2 microM, respectively. (+)-Canadine, with an IC50 value of 12.4 +/- 0.9 microM, was the most potent inhibitor of acetylcholinesterase, whilst (+/-)-corycavidine and (+)-bulbocapnine were effective inhibitors of butyrylcholinesterase with IC50 values of 46.2 +/- 2.4 microM and 67.0 +/- 2.1 microM, respectively. The other isolated alkaloids were considered inactive (IC50 > 100 microM).     

Isolation and cholinesterase activity of Amaryllidaceae alkaloids from Nerine bowdenii

Amaryllidaceae species are known as ornamental plants. Some contain galanthamine, an acetylcholinesterase inhibitor. The chemical composition of the alkaloid extract of bulbs of Nerine bowdenii Watson has been analyzed by means of GC/MS. Twenty-two compounds were detected and nineteen of them identified, one of which was belladine. The alkaloid extract showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 = 87.9 +/- 3.5 microg/mL) and human plasma butyrylcholinesterase (HuBuChE; IC50 = 14.8 +/- 1.1 microg/mL). Belladine inhibited HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 781 +/- 12.5 microM and 284.8 +/-4.2 microM, respectively.     

Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana

Three new prenylated xanthones, mangostenones C (1), D (2), and E (3), together with 16 known xanthones 4-19, were isolated from the young fruit (7-week maturity stage) of Garcinia mangostana. The structural elucidation of the new compounds was mainly established on the basis of 1D and 2D NMR and HR-MS spectroscopic analysis. Compound 1 showed cytotoxic properties against three human cancer cell lines, epidermoid carcinoma of the mouth (KB), breast cancer (BC-1), and small cell lung cancer (NCI-H187), with IC50 values of 2.8, 3.53, and 3.72 microg/ml, respectively. Among the isolates, alpha-mangostin (12), the major metabolite, exhibited the most potent effects against the BC-1 cells with an IC50 value of 0.92 microg/ml, an activity greater than that of the standard drug ellipticine (IC50 = 1.46 microg/ml). Compound 12 also showed the highest activity against KB cells, while gartanin (10) displayed the strongest activity against the NCI-H187 cells at the respective IC50 values of 2.08 microg/ml and 1.08 microg/ml.     

Cytotoxic and antimalarial prenylated xanthones from Cratoxylum cochinchinense

A new prenylated xanthone, 5-O-methylcelebixanthone (1), together with six known compounds; celebixanthone (2), 1,3,7-trihydroxy-2,4-di(3-methylbut-2-enyl)xanthone (3), cochinchinone A (4), alpha-mangostin (5), beta-mangostin (6) and cochinchinone C (7) were isolated from roots of Cratoxylum cochinchinense. Their structures were elucidated by spectroscopic methods. Compounds 2 and 4-7 showed cytotoxic activity against the human lung cancer cell line (NCI-H187) with IC(50) values ranging from 0.65 to 5.2 microg/ml. Compounds 1, 2, 6 and 7 also showed antimalarial activity against Plasmodium falciparum with IC(50) values of 3.2, 4.9, 7.2 and 2.6 microg/ml, respectively.     

COX-1, COX-2 inhibitors and antifungal agents from Croton hutchinsonianus

Two new compounds, 3'-(4'-hydroxy-3',5'-dimethoxyphenyl)-propyl benzoate (1) and 3'-(4'-hydroxyphenyl)-propyl benzoate (3) together with known compounds, 3'-(4'-hydroxy-3'-methoxyphenyl)-propyl benzoate (2), poilaneic acid (4), farnesyl acetone (5) and 4-hydroxybenzaldehyde (6) were isolated and identified from the branches of Croton hutchinsonianus. Their structures were determined by spectroscopic methods. The three phenylpropyl benzoates (1-3) were found to exhibit antifungal activity against Candida albicans (IC(50) 5.36-11.41 microg/ml). Compounds 1-2 (IC(50) 2.11-4.95 microg/ml) exhibited potent but non-selective activity against the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) whereas 3 (IC(50) 1.88 microg/ml) preferentially inhibited the enzyme COX-2.     

A new radical scavenging anthracene glycoside, asperflavin ribofuranoside, and polyketides from a marine isolate of the fungus microsporum

A new anthracene glycoside, asperflavin ribofuranoside (1), and the previously described polyketides, flavoglaucin (2), isodihydroauroglaucin (3), and citrinin (4) have been isolated from the marine-derived fungus Microsporum sp. The structure and absolute stereochemistry of a new compound (1) was assigned on the basis of physicochemical data. Compounds 1-3 exhibited a significant radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC(50) values of 14.2, 11.3, and 11.5 microM, respectively, which are more potent than the positive control, ascorbic acid (IC(50), 20 microM). Compound 1 also showed a moderate antibacterial activity against the methicillin-resistant and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA) with MIC value of 50 microg/ml.