A new cytotoxic indole alkaloid from Tabernaemontana inconspicua stapf.

One new indole alkaloid derivative, 5,6-dioxo-11-hydroxy voacangine (1) together with four known compounds (2-5), were isolated from the fruits of Tabernaemontana inconspicua Stapf (Apocynaceae). Their structures were determined using 1D and 2D NMR, HRESI-MS, and a comparison with the literature. The new compound was found to be cytotoxic on human breast cancer MDA-MB 231 cells with IC50 values of 3.35 µM and 2.19 µM after 24 and 48 hours, respectively.

Rapid and green analytical method for the determination of quinoline alkaloids from Cinchona succirubra based on Microwave-Integrated Extraction and Leaching (MIEL) prior to high performance liquid chromatography.

Quinas contains several compounds, such as quinoline alkaloids, principally quinine, quinidine, cinchonine and cichonidine. Identified from barks of Cinchona, quinine is still commonly used to treat human malaria. Microwave-Integrated Extraction and Leaching (MIEL) is proposed for the extraction of quinoline alkaloids from bark of Cinchona succirubra. The process is performed in four steps, which ensures complete, rapid and accurate extraction of the samples. Optimal conditions for extraction were obtained using a response surface methodology reached from a central composite design. The MIEL extraction has been compared with a conventional technique soxhlet extraction. The extracts of quinoline alkaloids from C. succirubra obtained by these two different methods were compared by HPLC. The extracts obtained by MIEL in 32 min were quantitatively (yield) and qualitatively (quinine, quinidine, cinchonine, cinchonidine) similar to those obtained by conventional Soxhlet extraction in 3 hours. MIEL is a green technology that serves as a good alternative for the extraction of Cinchona alkaloids.

Chemical composition of the essential oil of Cachrys libanotis from Algeria.

The essential oil of aerial parts of Cachrys libanotis L. (Apiaceae) from east Algeria was extracted by hydrodistillation and analyzed by GC-FID and GC-MS. Thirty-one compounds were identified, the main components being germacrene-D (18.0%), gamma-terpinene (6.4%), p-cymene (5.5%), caryophyllene oxide (5.1%), and limonene (5.1%).

Antimicrobial activity of the methanolic extract and compounds from the stem bark of Drypetes tessmanniana.

OBJECTIVE: To evaluate the antimicrobial activity of the methanol extract from the stem bark of Drypetes tessmanniana, fractions (DTB1-5) as well as compounds [friedelin (2), 3,7-dioxofriedelane (3), 3,15-dioxofriedelane (4), 3beta- O-(E)-3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene (6), and 3beta,6alpha-dihydroxylup-20(29)-ene (7). METHODS: Agar disc diffusion was used to determine the sensitivity of the above samples, whilst the microdilution method was used for the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentrations (MMC). RESULTS: The diffusion test showed that the crude extract was able to prevent the growth of all tested organisms. All other samples showed selective activity. The inhibitory effect of the fraction DTB2 was noted on 63.7%, that of DTB1 and DBT3 on 54.6%, whilst DTB4 and DTB5 were active on 9.1% of the 11 tested organisms. The tested compounds prevented the growth of 81.8% of the tested microbial species for compounds 3 and 4, 36.7% for compound 6, and 18.2% for compound 7. The results of the MIC determinations indicated perceptible values for DTB and compound 4 on 81.8% of the tested organisms. For other samples, MICs were detected on 0-63.7%. The lowest MIC value (78.12 microg/mL) for the crude extract and fractions (DTB2) was observed on M. audouinii. The corresponding value for isolated compounds (156.25 microg/mL) was noted with compounds 3 on S. faecalis and 4 on M. audouinii audouinii. The results of the MMC determination suggested that the microbicidal effect of most of the tested samples on the studied microorganisms could be expected. CONCLUSION: The methanol extract from the stem bark of Drypetes. tessmanniana (Euphorbiaceae) as well as some of the isolated compounds might be potential sources of new antimicrobial drugs.

Erymildbraedin A and B, two novel cytotoxic dimethylpyrano-isoflavones from the stem bark of Erythrina mildbraedii: evaluation of their activity toward endocrine cancer cells.

Two new dimethylpyrano-isoflavones, named erymildbraedin A (4) and B (5), were isolated from the stem bark of the Cameroonian medicinal plant Erythrina mildbraedii, along with four known ones, the linear congeners, scandenone (1), erysenegalinsein M (2), 5,4'-dihydroxy-2'-methoxy-8-(3,3-dimethylallyl)-2'',2''-dimethylpyrano[5,6:6,7]isoflavone (3), and the angular isoflavone eryvarin B (6), and two other compounds, fraxidin and scoparone. Their structures were elucidated by the usual spectroscopic methods and isoflavone effects on the growth of human breast, prostate, and endometrial adenocarcinoma cells were determined. Isoflavones 1, 3, and 6 strongly inhibited the growth of all three cell lines, supporting the notion that a non-oxidized isoprenyl group at C-8 is requisite for cytotoxic activity.

New friedelane triterpenoids with antimicrobial activity from the stems of Drypetes paxii.

Two new friedelane-type triterpenes named 12alpha-hydroxyfriedelane-3,15-dione and 3beta-hydroxyfriedelan-25-al, together with six known compounds were isolated from the stems of Drypetes paxii Hutch. (Euphorbiaceae). Their structures were established on the basis of conventional 1 dimensional (1D) NMR methods, 2D shift-correlated NMR experiments and mass spectra. The five friedelane-type triterpene derivatives and one olean-12-ene triterpene saponin were tested for antimicrobial activity against some gram-positive and gram-negative bacteria, and they appeared to be modestly active.

Triterpenoids with antimicrobial activity from Drypetes inaequalis.

The air-dried stems and ripe fruit of Drypetes inaequalis Hutch. (Euphorbiaceae) were studied. Four triterpene derivatives, characterized as lup-20(29)-en-3beta,6alpha-diol, 3beta-acetoxylup-20(29)-en-6alpha-ol, 3beta-caffeoyloxylup-20(29)-en-6alpha-ol and 28-betad-glucopyranosyl-30-methyl 3beta-hydroxyolean-12-en-28,30-dioate along with 10 known compounds were isolated from the whole stems. One triterpene, characterized as 3alpha-hydroxyfriedelan-25-al along with six known compounds were isolated from the ripe fruit. Their structures were established on the basis of spectroscopic analysis and chemical evidence. The triterpenes were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria, and two of them appeared to be modestly active.

New triterpenoids from the stem barks of Drypetes tessmanniana.

The MeOH extract of the stem barks of Drypetes tessmanniana (Euphorbiaceae) afforded two new triterpene derivatives characterized as 3beta-O-(E)-3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene and 3beta,6alpha-dihydroxylup-20(29)-ene together with seven known compounds. Their structures were established on the basis of spectral analysis.

Cytotoxic evaluation of sarcodifurines A and B, two novel dihydrofuroquinolines from Sarcomelicope follicularis (Rutaceae).

Sarcodifurines A and B are two original dihydrofuroquinolines isolated from Sarcomelicope follicularis, a New Caledonian tree. The cytotoxicity and antiproliferative activity of these two alkaloids were investigated against 8 distinct cell lines representative of the most frequent solid tumors developing in human. Cytotoxicity of sarcodifurines was low on the 8 cell lines, with, for example, less than 10% of the total cells killed after 24 h exposure at 10 microM and IC(50) approximately 7.10(-5) M (MCF-7 and MDA MB 231 cell lines). Proliferation studies confirmed that sarcodifurines had a weak effect on cancer cells growth, with less than 5% growth inhibition at 10 microM. Sarcodifurine A activity was comparable to that of Sarcodifurine B, in term of cytotoxicity and antiproliferative activity on all cell lines. In spite of the weak activity of sarcodifurines and furoquinolines, rationalized pharmacomodulations to obtain planar analogs could lead to efficient topoisomerases inhibitors and DNA intercalants.

Variability of two essential oils of Kundmannia sicula (L.) DC., a traditional Algerian medicinal plant.

The essential oils of the aerial parts of Kundmannia sicula (L.) DC collected from two Algerian localities, El Kala (near the coast) and Béjaia (from a meadow about 10 km from the coast), were analysed by GC and GC-MS. Although both samples showed similar overall chemical compositions, the major components of the Béjaia sample were identified as being spathulenol (14.8%), caryophyllene oxide (12.2%), salvial-4(14)en-1-one (10.1%), 1,5-epoxysalvial-4(14)ene (5.2%) and germacrene D (3.2%), while in the ElKala sample the main compounds were found to be salvial-4(14)en-1-one (16.4%), 1,5-epoxysalvial-4(14)ene (6.5%), chrysanthenyl acetate (5.2%) and alpha-amorphene (2.9%).

Antidepressant-like effect of hyperfoliatin, a polyisoprenylated phloroglucinol derivative from Hypericum perfoliatum (Clusiaceae) is associated with an inhibition of neuronal monoamines uptake.

This study investigated, in mice, the antidepressant like effect of hyperfoliatin, a prenylated phloroglucinol derivative isolated from the aerial parts of Hypericum perfoliatum, as well as its action on monoaminergic systems. In the forced-swimming test, hyperfoliatin dose-dependently reduced immobility time. Immobility was interpreted as an expression of "behavioural despair", which could be a component of depression syndrome. The effect of hyperfoliatin did not result from the stimulation of animal motor activity. Hyperfoliatin inhibited, in a concentration-dependent manner, the [(3)H]-dopamine, [(3)H]-serotonin and [(3)H]-noradrenaline synaptosomal uptakes, but did not prevent the binding of specific ligands to the monoamine transporters. These data suggest that the antidepressant-like effect of hyperfoliatin on the forced-swimming test is probably associated to monoamine uptake inhibition, due to a mechanism of action different from that of known antidepressants.

Isolation and partial characterization of antimicrobial compounds from a new strain Nonomuraea sp. NM94.

An actinomycete strain NM94 was isolated from a Saharan soil sample by a dilution agar plating method using chitin-vitamins B medium supplemented with penicillin. The strain presented the morphological and chemical characteristics of the genus Nonomuraea. On the basis of 16S rDNA analysis and physiological tests, this isolate was found to be quite different from the known species of Nonomuraea and might be new. The strain NM94 secreted several antibiotics on yeast extract malt extract glucose medium that were active against some Gram-positive bacteria, yeast, and fungi. The antibiotics were extracted with dichloromethane and detected by bioautography on silica gel plates using Mucor ramannianus and Bacillus subtilis as the test organisms. Among these antibiotics, a complex called 94A showed interesting antifungal activity. It was selected and purified by reverse-phase HPLC. This complex was composed of five compounds. Spectroscopic studies by infrared, mass, and (1)H NMR of the compounds were carried out. Initial results showed that these molecules differed from the known antibiotics produced by other Nonomuraea species.

Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series.

Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28. Cyclization gave the corresponding naphtho[1,2-b][1,10]-phenanthrolin-7(14H)-ones 29 and 30, and naphtho[1,2-b][1,7]-phenanthrolin-7(14H)-one 31, which were subsequently N-methylated to the desired 14-methylnaphtho[1,2-b][1,10] and [1,7]-phenanthrolinones 6, 7, and 8. Benzo[c]pyrano[3,2-h]acridin-7-one derivatives 3, 16, and 22 displayed cytotoxic activities within the same range of magnitude as acronycine itself, whereas 7-alkoxybenzo[c]pyrano[3,2-h]acridine and 7-acyloxybenzo[c]pyrano[3,2-h]acridine derivatives 4 and 17-21 were less active when tested against L1210 murine leukemia cells in vitro. Naphthophenanthrolinones 6-8 were devoid of significant antiproliferative activity, but compounds 29-31 bearing no substituent on the nitrogen atom at position 14 were more potent.

Pentacyclic triterpenoid and saponins from Gambeya boukokoensis.

Chemical studies of the EtOAc extract of Gambeya boukokoensis Aubr. et Pellegr. stem bark led to the isolation of eight compounds. Three of them were elucidated as new compounds and designated as: gamboukokoensein A, 1alpha,2alpha,3beta,19alpha,23-pentahydroxyurs-12-en-28-oic acid; gamboukokoenside A, 2beta,3beta,6beta,28-tetrahydroxyolean-12-en-23-oic acid 23-O-alpha-L-arabinopyranosyl ester and gamboukokoenside B, 6beta,28-dihydroxy-3-oxoolean-12-en-23-oic acid 23-O-alpha-L-arabinopyranosyl ester. The other five compounds were known and identified as myrianthic acid, protobassic acid, oleanolic acid, erythrodiol and chondrillasterol. Their structures were elucidated on the basis of one and two dimensional NMR spectroscopic techniques, FABMS, ESMS and chemical evidence.

A new polyisoprenylated phloroglucinol derivative from Hypericum perfoliatum (Clusiaceae).

Hyperfoliatin, a new polyisoprenylated phloroglucinol derivative was isolated from the aerial parts of Hypericum perfoliatum (Clusiaceae) collected in Algeria. The structure of hyperfoliatin was elucidated on the basis of its spectral data, mainly MS and multiple-pulse NMR.

Structure-activity relationships and mechanism of action of antitumor benzo[b]pyrano[3,2-h]acridin-7-one acronycine analogues.

The cytotoxic and antitumor activities of cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 3, 6-9 were strongly correlated with their ability to give covalent adducts with purified, as well as genomic, DNA. Such adducts involve reaction between the exocyclic N-2 amino group of guanines exposed in the minor groove of double helical DNA and the leaving ester group at the benzylic position 1 of the drug. A transesterification process of the ester group from position 2 to position 1 in aqueous medium accounted for the intense activity of the cis-1-hydroxy-2-acyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one derivatives 10-13. Compounds without acyloxy or hydroxy group at position 1, such as 15, 17, 18, and 22, were inert with respect to DNA and almost devoid of significant cytotoxic activity. Condensation of 5-amino-2,2-dimethyl-2H-chromene (26) with 3-bromo-2-naphthoic acid (27), followed by cyclization, gave access to 6-demethoxy analogues. Diacetate 32 and cyclic carbonate 33, both belonging to the latter series, were less reactive toward DNA and less cytotoxic than their 6-methoxy counterparts 3 and 34. DNA alkylation appears thus to play an important role in the antitumor properties of benzo[b]pyrano[3,2-h]acridin-7-one derivatives.

Phenolic constituents from Drypetes armoracia.

The methanol extract of the dried stem bark of Drypetes armoracia Pax & Hoffm. afforded two compounds named drypearmoracein A, (E)-4,5,6,7-tetrahydroxy-2-benzylhept-2-enoic acid and drypearmoracein B, 2,3-dihydroxy-9,10-tetrahydroanthra-1,4-quinone along with five known compounds: friedelan-3 beta-ol, friedelin, friedelane-3,7-dione, drypemolundein B and beta-stigmasterol. Their structures were established on the basis of spectroscopic analysis and chemical evidence.

Synthesis of 6-dialkylaminoalkylamino pyrano[2,3-c]acridones and benzo[b]pyrano[3,2-h]acridones: soluble acronycine analogues with increased cytotoxic activity.

The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones 5-11 and their benzo [b]pyrano[2,3-h]acridine-7-one counterparts 12-18 were prepared by treatment of acronycine (1) or benzo[b]acronycine (4) with an excess of the appropriate dialkylaminoalkylamine. In both series, the introduction of a dialkylaminoalkylamino side chain at position 6 resulted in a significant increase of the cytotoxic activity against L1210 cells when compared with the parent compounds bearing a methoxy group, accompanied with an increased potency to arrest cells in the G2 + M phases of the cell cycle.

New dithiolopyrrolone antibiotics from Saccharothrix sp. SA 233. I. Taxonomy, fermentation, isolation and biological activities.

Three new natural antibacterial and antifungal dithiolopyrrolone antibiotics were isolated along with the known iso-butyropyrrothine and thiolutine from the fermentation broth of an actinomycete strain which was isolated from a saharian palm grove soil collected at Adrar, south Algeria. The strain was identified as Saccharothrix sp. The three new antibiotics exhibited broad antimicrobial activity against gram-positive bacteria, yeasts and fungi in vitro.

New dithiolopyrrolone antibiotics from Saccharothrix sp. SA 233. II. Physicochemical properties and structure elucidation.

Three new natural dithiopyrrolone antibiotics, 3-methyl-2-butenoylpyrrothine (1), tigloylpyrrothine (2), and n-butyropyrrothine (3) were isolated along with the known isobutyropyrrothine (4) and thiolutin (5) from the fermentation broth of Saccharothrix sp. SA 233. The structures of the novel compounds were established on the basis on their spectral data.