ABSTRACT
Starting from three monomeric ergolines (terguride 1, festuclavine 2, pergolide 3) N,N'-spacer-linked oligomeric derivatives were prepared using different aliphatic or arylalkyl spacers. The compounds have been evaluated for their in vitro antiplasmodial activity against the chloroquine-sensitive strain poW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Additionally, the cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro, and human hepatocytes were evaluated. All monomers displayed only a weak antiplasmodial effect, but N-1,N-1'-spacer-linked dimerization substantially enhanced their antiplasmodial activity. The best activities were observed for compounds showing a distance of six carbon atoms between two monomers, which can be obtained by aliphatic or p-xylene linkers. The N-6,N-6'-spacer-linked depropylpergolide dimer 3i exhibited the highest antiplasmodial activity of all compounds tested (IC(50) values: 0.14 and 0.13 microM against poW and Dd2, respectively). Unfortunately, it displayed toxic effects against the mouse fibroblast cell line NIH 3T3 (IC(50): 0.1+/-0.09 microM) and also against human hepatocytes at 100 microM (LDH-leakage: 15.58+/-0.87 microkat/L; GSH-level: 8.15+/-0.78 nmol/10(6) cells). However, the N-1,N-1'-spacer-linked trimer of festuclavine (2f), and also the N-1,N-1'-spacer-linked tetramer of terguride (1g) possessed remarkable antiplasmodial activities (IC(50): 0.54 and 1.53 microM, respectively, against Dd2) lacking cytotoxicity.
Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Ergolines/chemistry , Ergolines/pharmacology , 3T3 Cells , Animals , Antimalarials/chemical synthesis , Cell Line , Ergolines/chemical synthesis , Humans , Inhibitory Concentration 50 , Mice , Molecular Structure , Plasmodium falciparum/drug effectsABSTRACT
Ten novel neo-clerodane diterpenoids, named cornutins C-L, have been isolated from the leaves of Cornutia grandifolia var. intermedia. Their structures have been elucidated by detailed spectroscopic analysis. In addition, the in vitro antiplasmodial activity of four isolated compounds (cornutin C-F) has been evaluated, revealing only a marginal activity.
Subject(s)
Diterpenes, Clerodane , Diterpenes/isolation & purification , Verbenaceae/chemistry , Animals , Antimalarials/chemistry , Antimalarials/isolation & purification , Antimalarials/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Leaves/chemistry , Plasmodium falciparum/drug effectsABSTRACT
The phytochemical investigation of the leaves of Siparuna pauciflora yielded three novel sesquiterpenoids: the germacrane sipaucin A, the elemane sipaucin B and sipaucin C, comprising a new type of carbon skeleton. In addition, four known aporphine alkaloids-nor-boldine, boldine, laurotetanine, and N-methyl-laurotetanine-were obtained. The evaluation of the antiplasmodial activity of the isolated compounds against two strains of Plasmodium falciparum (PoW, Dd2) showed a moderate activity of nor-boldine.
Subject(s)
Monimiaceae/chemistry , Sesquiterpenes/isolation & purification , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Magnetic Resonance Spectroscopy , Plant Leaves/chemistry , Plasmodium falciparum/drug effects , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
In this study the in vitro antiplasmodial activities of extracts from Cussonia spicata (Araliaceae), Artemisia afra, Vernonia colorata, V. natalensis (Asteraceae), Parinari curatellifolia (Chrysobalanaceae), Clutia hirsuta, Flueggea virosa, (Euphorbiaceae), Adenia gummifera (Passifloraceae) and Hymenodictyon floribundum, (Rubiaceae) were evaluated. The lipophilic extracts from the aerial parts of Artemisia afra and Vernonia colorata proved to be the most active against the chloroquine-sensitive strain PoW and against the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Bioassay-guided fractionation of the extract of A. afra yielded seven flavonoids, from which acacetin, genkwanin and 7-methoxyacacetin showed in vitro activity; the IC(50) values ranged from 4.3 microgram/mL to 12.6 microgram/mL. In addition, several sesquiterpene lactones could be obtained from the most active fractions. Whereas eudesmaafraglaucolide proved to be inactive, the guaianolides 1-desoxy-1alpha-peroxy-rupicolin A-8-O-acetate, 1alpha,4alpha-dihydroxybishopsolicepolide and rupicolin A-8-O-acetate revealed in vitro antiplasmodial activity. Evaluation of V. colorata gained four sesquiterpenes 11beta,13-dihydrovernodalin, vernodalol, 11beta,13-dihydrovernolide and 11beta,13,17,18-tetrahydrovernolide, from which the first two constituents exhibited the strongest antiplasmodial activity (IC(50) values: 1.1-4.8 microgram/mL).
Subject(s)
Antiprotozoal Agents/pharmacology , Malaria, Falciparum/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Plants, Medicinal , Plasmodium falciparum/drug effects , Animals , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/therapeutic use , Chloroquine , Drug Resistance , Humans , Inhibitory Concentration 50 , Medicine, African Traditional , Parasitic Sensitivity Tests , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Leaves , Plant Roots , Plant Stems , ZimbabweABSTRACT
From a methanolic extract of the leaves of Andira inermis (Fabaceae), andirol A and B, two compounds with a novel type of a rotenoid-related skeleton and andinermol, a new 2-aryl-3-hydroxymethyl-benzofuran could be isolated. Characterisation and structure elucidation of these compounds was achieved on the basis of their spectral data. In addition, the in vitro activities of the isolated compounds against both the chloroquine-sensitive strain PoW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum have been evaluated.
Subject(s)
Fabaceae/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Plant Extracts/chemistry , Aldehydes/chemistry , Aldehydes/isolation & purification , Benzofurans/chemistry , Benzofurans/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Magnetic Resonance Spectroscopy , Methanol , Models, Molecular , Molecular Conformation , Plant Extracts/isolation & purificationABSTRACT
Phytochemical re-investigation of the aerial parts of Bonamia spectabilis (Convolvulaceae) led to the isolation of four minor tetrahydrofuran-type sesquilignans (bonaspectins E-H) together with the known neolignan virolongin A and the known lignan rel-(7S,8R,7'R,8'R)-3,3',4,4',5,5'-hexamethoxylignan. Their structures were established on the basis of spectral data. These six compounds as well as further seven lignanoids from B. spectabilis, characterised previously, were tested for their antiplasmodial activity against a chloroquine-sensitive strain (PoW) and a chloroquine-resistant clone (Dd2) of Plasmodium falciparum. Bonaspectin C 4"-O-glucoside, its aglycone, and bonaspectin D 4"-O-glucoside revealed the highest antiplasmodial activities (IC50 values: 1.3, 2.0, 6.5 microM [PoW]; 1.7, 4.6, 3.7 microM [Dd2], respectively).
Subject(s)
Antimalarials/pharmacology , Convolvulaceae/chemistry , Lignans/chemistry , Lignans/pharmacology , Plasmodium falciparum/drug effects , Animals , Antimalarials/chemistry , Chloroquine/pharmacology , Drug Resistance , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
A lipophilic extract of the root bark of Stereospermum kunthianum revealed antiplasmodial activity in vitro. Bioassay-guided fractionation led to the isolation of four novel naphthoquinones (sterekunthals A and B, pyranokunthones A and B) and one novel anthraquinone (anthrakunthone) together with the known naphthoquinone pinnatal. The structures of the novel compounds were determined by comprehensive analyses of their 1D and 2D NMR data. The antiplasmodial activities and toxicity against the endothelial cell line ECV-304 of the isolated compounds have been assessed.
Subject(s)
Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Bignoniaceae/chemistry , Naphthoquinones/isolation & purification , Naphthoquinones/pharmacology , Plasmodium falciparum/drug effects , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/toxicity , Cell Line , Endothelium/cytology , Endothelium/drug effects , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Malaria/drug therapy , Molecular Structure , Naphthoquinones/chemistry , Naphthoquinones/toxicity , Plant Bark/chemistry , Plant Roots/chemistryABSTRACT
Different extracts from 11 West African plants traditionally used against malaria in Ghana were tested against both the chloroquine-sensitive strain PoW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Due to the promising in vitro activity of the lipophilic extract [IC50: 10.5 microg/ml (PoW); 13.1 microg/ml (Dd2)], Microglossa pyrifolia (Lam.) Kuntze (Asteraceae) was chosen for further phytochemical investigation. From active fractions 13 compounds were isolated; their structures were established on the basis of spectroscopic methods. 1-Acetyl-6E-geranylgeraniol-19-oic acid and sinapyl diangelate represent new natural compounds. The two diterpenes E-phytol [IC50: 8.5 microM (PoW); 11.5 microM (Dd2)], and 6E-geranylgeraniol-19-oic acid [IC50: 12.9 microM (PoW); 15.6 microM (Dd2)] proved to be the most active constituents in our test system.
