Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part I: Aspidosperma nitidum (Benth) used as a remedy to treat fever and malaria in the Amazon

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.     

Structure-Activity Relationship of Benzophenanthridine Alkaloids from Zanthoxylum rhoifolium Having Antimicrobial Activity

Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1–3), and nine benzophenanthridine alkaloids (4–12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced oxidized protein products) levels when compared to the control group.     

Alkaloids and an acetylenic lactone from the stem bark of Sapranthus palanga

In addition to the known alkaloids 9S-sebiferine and liriodenine the stem bark of Sapranthus palanga has yielded the novel acetylenic lactone sapranthin. Primarily on the basis of spectral data sapranthin has been identified as 3-(hexadeca-11,15-diena-7,9-diynyl)4-hydroxy-5-methyltetrahydrofuran-2-one.     

Indole alkaloids from a callus culture of Tabernaemontana elegans

Fourteen indole alkaloids have been isolated from a callus culture of Tabernaemontana elegans. One of them is new, 3-oxo-isovoacangine, the others are the known isovoacangine, 3-R/S-hydroxy-isovoacangine, 3-R/S-hydroxy-coronaridine, isositsirikine, geissoschizol, tabernaemontanine, vobasine, vobasinol, apparicine, 16-hydroxy-16,22-dihydro-apparicine, tubotaiwine, 3-R/S-hydroxy-conodurine and monogagaine. The alkaloid content is similar to that of the whole plant, except for the absence ofthe tabernaelegantines, which were major components in the plant extract.     

Dehydroisostrychnobiline,matopensine and other alkaloids from Strychnos kasengaensis

Eighteen alkaloids have been identified in the root bark, stem bark and leaves of Strychnos kasengaensis from Zaire, They are isoretulinal, retuline, desacetyl isoretuline, desacetyl retuline, dehydroisostrychnobiline, matopensine and its mono-N-oxide, nordihydrotoxiferine, isoretuline, N(1)-desacetyl 18-acetoxyisoretuline, Wieland-Gumlich aldehyde and diol, desacetyl isoretulinal, O-acetyl retuline, 16R-isositsirikine, O-acetyl isoretuline, 11-methoxy retuline and 11-methoxy isoretuline.     

Alcaloïdes indoliniques du Strychnos variabilis

Three new indolinic alkaloids have been isolated from the root bark of Strychnos variabilis: strychnopivotine, unusual because the C₁₇ atom of the curane skeleton is lacking, 16-hydroxyisoretulinal and rosibiline, a derivative of N-desacetylretuline. Their structures were deduced from spectral data and that of rosibiline was confirmed chemically.     

Alcaloides d'Araliopsis soyauxii. Isolement d'un nouvel alcaloide,l'Araliopsine

Six alkaloids have been isolated from root bark of Araliopsis soyauxii. Five are known, maculine, flindersiamine, skimmianine, (?) ribalinine, (+) isoplatydesmine and the sixth, araliopsine is new; its structure has been established as hydroxyisopropyldihydrofuro-2-quinolone. From the trunk bark four alkaloids have been isolated: flindersiamine, kokusaginine (?) ribalinine, (+) isoplatydesmine.     

Prenylated indole alkaloids from the stem bark of Hexalobus monopetalus

Seven new prenylated indole alkaloids (1–7) together with two known compounds (8–9) were isolated from the stem bark of Hexalobus monopetalus. Their structures were established on the basis of comprehensive spectroscopic analysis, including HR-MS, 1D and 2D NMR and by comparison of their spectral data with those reported in literature. The new compounds were tested for antimicrobial activity against selected pathogenic bacteria and fungi but showed no activity. The marked presence of prenylated indole alkaloids in Hexalobus and closely related genera makes them useful chemotaxonomic markers.     

New erythrina alkaloids of Cocculus laurifolia

Four abnormal Erythrina alkaloids have been isolated from the leaves of Cocculus laurifolia. Of these, two new bases, isococculidine and coccoline, have been assigned the structures (3S,5S)-3,15-dimethoxyerythrin-1-ene and (3R,5S)-15-hydroxy-3-methoxyerythrin-1-en-8-one respectively.     

Dimeric bisindole alkaloids from the stem bark of Strychnos nux-vomica L.

Strychnos nux-vomica L. (Loganiaceae) is famous for its monomeric alkaloid content, such as strychnine, a convulsant poison. The stem bark of the tree is traditionally used to treat intermittent fever in South East Asia. In various studies, it appeared that dimeric indolo-monoterpenic alkaloids possess a promising activity on Plasmodium falciparum. Three bisindolomonoterpenic alkaloids together with strychnochrysine, previously identified in the root bark of S. nux-vomica, were isolated from the stem bark. The structures of these compounds were established using NMR spectroscopy and mass spectrometry.Stereochemistry of the compounds was confirmed by molecular modelling. This then allowed the structural determination of strychnoflavine, a coloured bisindole alkaloid previously isolated from the root bark of the tree. Moreover, the conformational inversion in alkaloids possessing an ether bond in the strychnane moiety could be easily predicted by specific δ ¹³C NMR values.These longicaudatine-type alkaloids were found to display in vitro antiplasmodial activity against a chloroquine resistant strain and a chloroquine sensitive strain. The most interesting was strychnochrysine showing an IC₅₀ value at around 10 μM.     

Two new diterpenoids from Plectranthus species

Two new diterpenoids, ent-7α-acetoxy-15-beyeren-18-oic acid and (13S,15S)-6β,7α,12α,19-tetrahydroxy-13β,16-cyclo-8-abietene-11,14-dione, have been isolated from Plectranthus saccatus and Plectranthus porcatus, respectively, and their structures were established by 1D and 2D NMR spectroscopic studies. The new diterpenes showed no activity against Gram-negative bacteria and Candida albicans (yeast strain). Among Gram-positive bacteria, the lower MIC value was 62.50 μg/ml for the abietane derivative against Staphylococcus aureus ATCC 6538.     

Quinoline and indolopyridoquinazoline alkaloids from Vepris louisii

The structures of two new 2-quinolone alkaloids from the stem bark of Vepris louisii, N-methylpreskimmianine [7,8 - dimethoxy - 3 - (3 - methylbut - 2 - enyl) - 1 - methyl - 2 - quinolone] and veprisine (7,8 - dimethoxy - N - methylflindersine) have been deduced from their spectral data and confirmed by partial synthesis from known compounds. Two minor indolopyridoquinazoline alkaloids were also isolated and identified as the already known 1-hydroxyrutaecarpine and the hitherto unknown 7,8-dehydro derivative of 1-hydroxyrutaecarpine.     

Alkaloids from Melodinus yunnanensis

Ten monoterpenoid indole alkaloids, namely meloyine, 19S-methoxytubotaiwine N₄-oxide, 16,19-epoxy-Δ¹⁴-vincanol, 14β-hydroxymeloyunine, meloyunine, Δ¹⁴-vincamenine N₄-oxide, 16β,21β-epoxy-vincadine, 14β,15β-20S-quebrachamine, 3-oxo-voaphylline, 2α,7α-dihydroxy-dihydrovoaphylline, and 32 known alkaloids were isolated from leaves and twigs of Melodinus yunnanensis. Their structures were elucidated based on 1- and 2-D NMR, FTIR, UV, and MS spectroscopic data. Meloyine I showed weak cytotoxic activity against four human cancer cell lines: MCF-7 breast cancer, SMMC-7721 hepatocellular carcinoma, HL-60 myeloid leukemia, and A-549 lung cancer.     

Sesquiterpenes and alkaloids from Cleistopholis patens

The root bark of Cleistopholis patens collected in Ghana yielded two sesquiterpenes and five alkaloids. The sesquiterpenes have been characterised as the acyclic methyl-(?)-(trans)-(trans)-10,11-dihydroxyfarnesoate and its monocyclic derivative methyl-(+)-10-hydroxy-6,11-cyclofarnes-7(14)-enoate. The alkaloids were of the unusual aza-polycyclic and naphthyridine groups and included one new member of both classes. Examination of stem bark samples from the same source and from Sierre Leone showed the presence of the sesquiterpenes and the oxoaporphine alkaloid liriodenine but neither of the rarer alkaloid types.     

Alkaloids of Sri Lankan Strychnos nux-vomica

Twenty-two identified alkaloids have been isolated from the root bark and leaves of a Sri Lankan Strychnos species supplied as S. nux-vomica. T     

Further alkaloids of Alstonia muelleriana

Five further alkaloids, des-N′_a-methylanhydromacralstonine, quebrachidine, vinervinine, pleiocarpamine, and 2,7-dihydropleiocarpamine, have been isolated from Alstonia muelleriana bark. Phytochemical problems in the genus Alstonia are considered, especially with reference to the ‘macroline-derived’ indole and bis-indole alkaloids.     

16-epi-19-S-vindolinine,an indoline alkaloid from Catharanthus roseus

Studies on the alkaloids of Catharanthus roseus have resulted in the isolation of a new alkaloid, to which the structure of 16-epi-19-S-vindolinine has been assigned.     

Alkaloids,limonoids and furocoumarins from three Mexican Esenbeckia species

The chemical constituents of three Mexican Esenbeckia species have been determined. Rutaevin was the main limonoid present in the seeds of all three species, E. litoralis, E. flava and E. berlandieri. The husks, leaves, wood and bark contained a wide array of known furocoumarins and furoquinoline alkaloids. In addition, 1-hydroxy-3-methoxy-N-methylacridone was obtained from E. litoralis bark and a new natural 2-quinolone alkaloid, formulated as 3,3-diisopropyl-N-methyl-2,4-quinoldione, was obtained from E. flava wood. The structure was assigned from spectroscopic considerations and conversion to N-methylhaplofoline.     

3S,24S,25-Trihydroxytirucall-7-ene from Ailanthus excelsa

A new triterpene has been isolated from the root bark of Ailanthus excelsa (Simaroubaceae) and identified as 3S,24S,25-trihydroxytirucall-7-ene.     

Alkaloids of Alstonia macrophylla

A new alkaloid, 19-hydroxyvincamajine, has been isolated from the leaves of Alstonia macrophylla. In addition to this, eight other indole alkaloids, alstonerine, alstophylline, macralstonine, anhydromacralstonine, talcarpine, vincamajine, vincorine and cabucraline, were also isolated and identified from the bark and leaves of A. macrophylla of Sri Lanka. The last five alkaloids have been isolated for the first time from this species and the ¹³NMR of alstonerine and alstophylline are reported.