Anti-cancerous triterpenoid saponins from Lecaniodiscus cupanioides.

From the ethanol extract of the stem of Lecaniodiscus cupanioides Planch, two known compounds 1 and 2 were isolated and identified as triterpenoid saponins 3-O-[α-L-arabinofuranosyl- (1→3)-α-L-rhamnopyranosyl- (1→2)-α-L-arabinopyranosyl-]-hederagenin and 3-O- [α-L-arabinopyranosyl- (1→3)-α-L-rhamnopyranosyl (1→2)-α-L-arabinopyranosyl-]-hederagenin. The structures were established by physicochemical and spectroscopic investigations (MS and NMR) as well as comparison of literature data. The compound 1 exhibited anticancer activity against human colon carcinoma H-116, human lung carcinoma A-549 and human lung carcinoma HT-29 cell lines with IC50 5.0, 2.5 and 2.5µg/ml respectively and compound 2 exhibited similar activities with IC505.0, 5.0 and 2.5µg/ml respectively. This suggests that the isolated triterpenoid saponins may be considered as potential anticancer leads for further studies.

In vitro evaluation of aliphatic fatty alcohol metabolites of Perseaamericana seed as potential antimalarial and antimicrobial agents.

Perseaamericana Mill (Lauraceae) is a local medicinal plant used in Nigerian ethnomedicine as antimalarial. The aqueous decoction of the root part is a potent remedy against bacterial infections. Hence, the need to investigate the phytochemical and biological activities (antimicrobial and antiplasmodial) of the root back of Perseaamericana. Chromatographic and spectroscopic techniques were used in the identification and purification of metabolites, which were assayed for antimalarial and antimicrobial activities using Plasmodium falciparum and a panel of microorganisms. From the seeds of P. americana, five known 1, 2, 4-dihydroxy derivatives aliphatic alcohols, called avocadenols were isolated and identified by spectroscopic methods including 1D- and 2D NMR, and comparison with reported data in literature. Antifungal activity for 1, 2, 4-Trihydroxyheptadec-6-en-16-yne (5) (IC50< 8 µg/mL) against all the fungal strains and S. areus, and antimalarial activity for compounds 1, 2, 4-Trihydroxyheptadec-16-ene (1) and 1, 2, 4-tetrahydroxyheptadecane-6, 16-diene(2) (IC50 = 1.6 and 1.4 µg/mL for the D6 clone, respectively, and 2.1 and 1.4 µg/mL for the W2 clone, respectively) was observed. The fatty alcohols 1, 2, 4-tetrahydroxyheptadecane-6, 16-diene(2); 1, 2, 4-Trihydroxyheptadec-16-yne(3) and 1, 2, 4-Trihydroxyheptadecane(4) also exhibited promising in vitro antibacterial activity against a panel of pathogenic bacteria S. areus, methicillin resistant S. areus and E. coli at IC50 values of 21.1, 8, 200 µg/mL), (3.259, 86.32 µg/mL) and (17.18, 8.26 and 200 µg/mL), respectively. The results of this study provide evidence that the fatty alcohols are a promising class of antimalarial and antimicrobial agents.

Phytosterols from Spondias mombin Linn with Antimycobacterial Activities.

The growing problems of tuberculosis have led to the search for new anti-Mtb agents from higher plants. The stem bark of Spondias mombin was evaluated for its in vitro activity against Mycobacterium tuberculosis (H37Rv strain). Bioassay-guided fractionation of the methanol extract was carried out by Vacuum Liquid Chromatography (VLC) on Silica gel (230-400 mesh) and purification was done using HPLC and TLC. In vitro antimycobacterial susceptibility was performed by a fluorometric microplate alamar blue assay (MABA) and percentage mycobacterial inhibition was calculated. The structures of the isolated compounds were established by spectroscopic analysis. The active VLC fraction exhibited 91% inhibition against M. tuberculosis H37Rv at a concentration of 40 µg/mL. The HPLC fraction SMi-15 containing compounds 1 and 2 showed 92.8% inhibition against M. tuberculosis. Two new antimycobacterial phytosterols were isolated from the stem bark of S. mombin and the structures were identified as mombintane I (1) and mombintane II (2). The stem bark extractives of S. mombin contain antitubercular principles of the class phytosterol and support an important potential of triterpenoids.

Marine natural products as lead anti-HIV agents.

Current anti-HIV drugs have extreme side effects and resistance to these drugs develops rapidly. The marine environment holds an unprecedented number of unusual chemical structural classes with activity against HIV. We review the literature on anti-HIV activity of marine natural products and discuss the efficacy of different structural classes.

Isolation of an antifreeze peptide from the Antarctic sponge Homaxinella balfourensis.

Polar plants and animals survive in subzero waters (-2 degrees C) and many of these marine organisms produce antifreeze proteins (AFPs) to better adapt themselves to these conditions. AFPs prevent the growth of ice crystals which disrupt cellular membranes and destroy cells by inhibiting crystallization of water within the organism. The hydrophilic extract of an Antarctic sponge Homaxinella balfourensis exhibited a non-colligative freezing point depression effect on the crystal morphology of water. The extract was purified by repeated reverse phase high-pressure liquid chromatography, then assayed and shown to contain several AFPs. The major peptide was isolated, analyzed using matrix-assisted laser desorption ionization mass spectrometry and the partial structure of the peptide identified through amino acid sequencing. AFPs have potential applications in agriculture, medicine and the food industry.

Isolation and biological evaluation of filiformin, plakortide F, and plakortone G from the Caribbean sponge Plakortis sp.

The bioassay- and spectroscopic-guided fractionation of the antimalarial extract from a Jamaican sponge, Plakortis sp., resulted in the isolation of three metabolites. The previously reported bromoaromatic filiformin (1) was obtained from our sample of Plakortis sp., and the potential origins of this compound are discussed. The peroxide-containing metabolite, plakortide F (2), is a more typical Plakortis metabolite and was shown to exhibit significant activity against Plasmodium falciparum in vitro. The isolation, structure, and bioactivity of a new lactone, plakortone G (3), are also reported.

New manzamine alkaloids with potent activity against infectious diseases.

The isolation of the new enantiomers of 8-hydroxymanzamine A (1), manzamine F (2), along with the unprecedented manzamine dimer, neo-kauluamine from an undescribed genus of Indo-Pacific sponge (family Petrosiidae, order Haplosclerida) is reported. The relative stereochemistry of neo-kauluamine was established through detailed analysis of NOE-correlations combined with molecular modeling. The significance of the manzamines as in vivo antimalarial agents with superior activity to the clinically used drugs artemisinin and chloroquine is discussed along with the activity in vitro against the AIDS-opportunistic infectious diseases tuberculosis and toxoplasmosis. Reexamination of the sponges identified as Prianos, and Pachypellina, in earlier publications has confirmed that these are members of the same genus as the sponge described here, but differ at the species level.

Antimalarial, antiviral, and antitoxoplasmosis norsesterterpene peroxide acids from the Red Sea sponge Diacarnus erythraeanus.

A new norsesterterpene acid, named muqubilone (1), along with the known sigmosceptrellin-B and muqubilin were isolated from the Red Sea sponge Diacarnus erythraeanus. The structure determination of 1 was based primarily on 1D and 2D NMR analyses. Sigmosceptrellin-B exhibits significant in vitro antimalarial activity against Plasmodium falciparum (D6 and W2 clones) with IC(50) values of 1200 and 3400 ng/mL, respectively. Muqubilin and 1 show in vitro antiviral activity against herpes simplex type 1 (HSV-1) with ED(50) values of 7.5 and 30 microg/mL, respectively. Muqubilin and sigmosceptrellin-B display potent in vitro activity against Toxoplasma gondii at a concentration of 0.1 microM without significant toxicity.

A new bisabolene derivative from the essential oil of Prangos uechtritzii fruits.

The fruits of endemic Prangos uechtritzii Boiss. & Hausskn. (Umbelliferae) were subjected to hydrodistillation and microdistillation. The resulting volatiles were investigated by GC-MS to determine the composition of the essential oils. 109 compounds representing 86.7% and thirty-two compounds representing 90.0% were identified and isolated by two different techniques, respectively. Column chromatography of the essential oil yielded a new bisabolene ether (7-epi-1,2-dehydrosesquicineole), which was characterized by spectral methods (GC-FTIR, 1D-, 2D NMR and HRESIMS).

Biotransformation of the antimelanoma agent betulinic acid by Bacillus megaterium ATCC 13368.

Microbial transformation of the antimelanoma agent betulinic acid was studied. The main objective of this study was to utilize microorganisms as in vitro models to predict and prepare potential mammalian metabolites of this compound. Preparative-scale biotransformation with resting-cell suspensions of Bacillus megaterium ATCC 13368 resulted in the production of four metabolites, which were identified as 3-oxo-lup-20(29)-en-28-oic acid, 3-oxo-11alpha-hydroxy-lup-20(29)-en-28-oic acid, 1beta-hydroxy-3-oxo-lup-20(29)-en-28-oic acid, and 3beta,7beta, 15alpha-trihydroxy-lup-20(29)-en-28-oic acid based on nuclear magnetic resonance and high-resolution mass spectral analyses. In addition, the antimelanoma activities of these metabolites were evaluated with two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).

New caryophyllene derivatives from Betula litwinowii.

Four new caryophyllene derivatives-14-hydroxy-4, 5-dihydro-beta-caryophyllene (1), 14-acetoxy-4, 5-dihydro-beta-caryophyllene (2), 4, 5-dihydro-beta-caryophyllene-14-al (3), and caryophylla-8(14)-en-5-one (4)-are reported from the essential oil of Betula litwinowii. Compounds 1-4 were characterized by MS and 1D and 2D NMR analyses and chemical transformations. The antibacterial and antifungal activity of 1 is also reported.

In vivo antimalarial activity of the beta-carboline alkaloid manzamine A.

Manzamine A, a beta-carboline alkaloid present in several marine sponge species, inhibits the growth of the rodent malaria parasite Plasmodium berghei in vivo. More than 90% of the asexual erythrocytic stages of P. berghei were inhibited after a single intraperitoneal injection of manzamine A into infected mice. A remarkable aspect of manzamine A treatment is its ability to prolong the survival of highly parasitemic mice, with 40% recovery 60 days after a single injection. Oral administration of an oil suspension of manzamine A also produced significant reductions in parasitemia. The plasma manzamine A concentration peaked 4 h after injection and remained high even at 48 h. Morphological changes of P. berghei were observed 1 h after treatment of infected mice. (-)-8-Hydroxymanzamine A also displayed antimalarial activity, whereas manzamine F, a ketone analog of manzamine A, did not. Our results suggest that manzamine A and (-)-8-hydroxymanzamine A are promising new antimalarial agents.

Mololipids, a new series of anti-HIV bromotyramine-derived compounds from a sponge of the order verongida.

A new series of lipids called mololipids have been identified from an Hawaiian sponge of the order Verongida. The structures of these lipids was deduced from spectroscopic data of the lipid mixture combined with GC-MS analysis. The core of this novel series of lipids is a bromotyramine homoserine-derived moiety known as moloka'iamine (1) which is found in many Verongid sponge metabolites. Moloka'iamine forms bisamides with a diverse series of fatty acids and the mololipids mixture (2) was active against HIV-1 with an EC(50) of 52.2 microM without cytotoxicity in human lymphocytes (IC(50) > 100 microM).

Dimerization of resveratrol by the grapevine pathogen Botrytis cinerea.

Resveratrol (trans-3,4',5-trihydroxystilbene) is produced by grapes (Vitis spp.) in response to microbial attack by the fungal grapevine pathogen Botrytis cinerea. Several reports indicate that pathogenic B.cinerea strains are capable of biotransforming resveratrol into an assortment of unidentified oxidized metabolites as a means of reducing the antifungal effects of resveratrol and facilitating Botrytis invasion into host-plant tissues. Studies utilizing growing incubations of Botrytis cinerea ATCC 11542 with resveratrol resulted in the production of three new (restrytisols A-C) (1-3) and three known (resveratrol trans-dehydrodimer, leachinol F, and pallidol) oxidized resveratrol dimers. All of the metabolites were evaluated for their anti-HIV-1, cytotoxic, and cyclooxygenase (COX) I and COX II inhibitory activities.

Microbial transformations of the antimelanoma agent betulinic acid.

Microbial transformation studies of the antimelanoma agent betulinic acid (1) were conducted. Screening experiments showed a number of microorganisms capable of biotransforming 1. Three of these cultures, Bacillus megaterium ATCC 14581, Cunninghamella elegans ATCC 9244, and Mucor mucedo UI-4605, were selected for preparative scale transformation. Bioconversion of 1 with resting-cell suspensions of phenobarbital-induced B. megaterium ATCC 14581 resulted in the production of the known betulonic acid (2) and two new metabolites: 3beta,7beta-dihydroxy-lup-20(29)-en-28-oic acid (3) and 3beta,6alpha, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (4). Biotransformation of 1 with growing cultures of C. elegans ATCC 9244 produced one new metabolite characterized as 1beta,3beta, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (5). Incubation of 1 with growing cultures of M. mucedo UI-4605 afforded metabolite 3. Structure elucidation of all metabolites was based on NMR and HRMS analyses. In addition, the antimelanoma activity of metabolites 2-5 was evaluated against two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).

Characterization of 6-epi-3-anhydroophiobolin B from Cochliobolus heterostrophus.

The new sesterterpenoid 6-epi-3-anhydroophiobolin B (1) and six known ophiobolins were isolated from the extracts of the fungus Cochliobolus heterostrophus race O. The structure of 6-epi-3-anhydroophiobolin B was deduced from analysis of spectral data and the structural characterization of dehydration and dimerization products. Ophiobolin A (2) showed potent activity in cytotoxicity assays and marginal activity in antimalarial assays.

Chemistry of puupehenone: 1,6-conjugate addition to its quinone-methide system.

The marine natural product puupehenone (1), isolated in good yields from sponges of the genus Hyrtios, has been shown to undergo stereospecific 1,6-conjugate addition to its quinone-methide system. Several nucleophilic agents such as hydrogen cyanide, Grignard reagents, and nitroalkanes were studied, producing structurally diverse compounds. This lead optimization study was initiated due to the bioactivity of puupehenone and its natural analogues, which includes numerous previous reports of potential anticancer and antiinfective activity.

Debromosceptrin, an alkaloid from the Caribbean sponge Agelas conifera.

As the result of a structurally guided isolation to identify lead compounds for the treatment of opportunistic infections of AIDS, the dihydrochloride salt of a new symmetrical pyrrole dimer debromosceptrin (1), and two known pyrrole analogues (2 and 3) were isolated from the Caribbean sponge Agelas coniferacollected from Belize. The structure of debromosceptrin was identified by analysis of spectral data. 15N spectral data assignments were made for compounds 1-3. Compounds 2 and 3 showed marginal inhibition of Mycobacterium tuberculosis.

Debromosceptrin, an alkaloid from the Caribbean sponge Agelas conifera

As the result of a structurally guided isolation to identify lead compounds for the treatment of opportunistic infections of AIDS, the dihydrochloride salt of a new symmetrical pyrrole analogues (2 and 3) were isolated from the Caribbean sponge Agelas conifera collected from Belize. The structure of debromosceptrin was identified by analysis of spectral data. 15N spectral data assignments were made for compounds 1-3. Compounds 2 and 3 showed marginal inhibition of Mycobacterium tuberculosis (Au)

New pyrrole alkaloids from Solanum sodomaeum.

Two new pyrrole alkaloids, solsodomine A and B, were isolated from the fresh berries of Solanum sodomaeum L., collected from the Libyan desert. The structures of these compounds were established by 2D-NMR, including 15N NMR spectroscopy and chemical degradation. Solsodomine A (1) shows activity against Mycobacterium intracellulare. This is the first report of pyrrole alkaloids from the genus Solanum.