New manzamine alkaloids with activity against infectious and tropical parasitic diseases from an Indonesian sponge

Eleven manzamine type alkaloids, two beta-carbolines, and five nucleosides have been isolated from an Indonesian sponge. Among these are the previously characterized 12,34-oxamanzamine A, 12,34-oxamanzamine E, manzamine A (1), 8-hydroxymanzamine A, 6-deoxymanzamine X, manzamine E (2), manzamine X, manzamine F (4), norharman, thymine, 2',3'-didehydro-2',3'-dideoxyuridine, uracil, thymidine, and 2'-deoxyuridine. The structures for the five new compounds have been assigned as 32,33-dihydro-31-hydroxymanzamine A (3), 32,33-dihydro-6-hydroxymanzamine A-35-one (5), des-N-methylxestomanzamine A (6), 32,33-dihydro-6,31-dihydroxymanzamine A (7), and 1,2,3,4-tetrahydronorharman-1-one (8), on the basis of NMR and X-ray data. The bioactivity and SAR of the manzamines against malaria, TB, and leishmania are also presented. The structural revision of two previously reported pyrazoles as uracil and thymine is also discussed.     

Three new manzamine alkaloids from a common Indonesian sponge and their activity against infectious and tropical parasitic diseases

Three new manzamine-type alkaloids, 12,34-oxamanzamine E (3), 8-hydroxymanzamine J (4), and 6-hydroxymanzamine E (8), as well as 12 previously characterized manzamine alkaloids have been isolated from a common Indonesian sponge of the genus Acanthostrongylophora. The structures of the new compounds have been established on the basis of 1D and 2D NMR spectroscopic analysis and comparison of the data to literature values of related compounds. The biological activities and structure-activity relationship of the manzamines against malaria, Mycobacterium tuberculosis, Leishmania, HIV-1, and AIDS opportunistic infections are discussed. A plausible pathway for the formation of the 12,34-oxaether bridge in compound 3 is also provided.     

Suberedamines A and B, new bromotyrosine alkaloids from a sponge Suberea species

Two new cytotoxic bromotyrosine alkaloids, suberedamines A (1) and B (2), have been isolated from an Okinawan marine sponge Suberea sp. The structures were elucidated on the basis of spectroscopic data and chemical means.     

Naamidines H and I, cytotoxic imidazole alkaloids from the Indonesian marine sponge Leucetta chagosensis

Two new imidazole alkaloids, naamidines H ( 1) and I ( 2), were isolated from the marine sponge Leucetta chagosensis, collected in North Sulawesi, Indonesia. The compounds ( 1 and 2) showed cytotoxicity against HeLa cells with IC50 values of 5.6 and 15 microg/mL, respectively.     

Arenosclerins A-C and haliclonacyclamine E, new tetracyclic alkaloids from a Brazilian endemic Haplosclerid sponge Arenosclera brasiliensis

Arenosclerins A (2), B (3), and C (4), as well as haliclonacyclamine E (1), are new tetracyclic alkylpiperidine alkaloids isolated from a new species of marine sponge belonging to the order Haplosclerida, Arenosclera brasiliensis, a species endemic to the southeastern Brazilian coast. The alkaloids were isolated as their hydrochloride salts and identified by analysis of spectroscopic data. Data obtained from (1)H-(1)H COSY, HMBC, and HSQC-TOCSY NMR experiments allowed complete assignment of the (1)H and (13)C resonances, and analysis of the NOESY and ROESY spectra showed that the only differences between 2, 3, and 4 were the relative stereochemistries of the bispiperidine ring system. Arenosclerins A-C are the first haliclonacyclamine/halicyclamine-related alkaloids with a hydroxy group in the bridging alkyl chain.     

Pordamacrines A and B, alkaloids from Daphniphyllum macropodum

The new Daphniphyllum alkaloids, pordamacrines A (1) and B (2), have been isolated from the leaves of Daphniphyllum macropodum, and their structures were elucidated on the basis of interpretation of spectroscopic data and by the single-crystal X-ray diffraction analysis of 2. Pordamacrines A (1) and B (2) exhibited moderate vasorelaxant effects on the rat aorta.     

Hipposulfates A and B, new sesterterpene sulfates from an Okinawan sponge, Hippospongia cf. metachromia

Two new sesterterpene sulfates, hipposulfates A (1) and B (2), have been isolated from an Okinawan sponge, Hippospongia cf. metachromia and their structures elucidated by interpretation of spectroscopic data. Both compounds contain an enolsulfate functionality. Hipposulfate A (1) showed moderate cytotoxicity.     

Tetradehydrohalicyclamine A and 22-hydroxyhalicyclamine A, new cytotoxic bis-piperidine alkaloids from a marine sponge Amphimedon sp

Two new 3-alkylpiperidine alkaloids, tetradehydrohalicyclamine A (2) and 22-hydroxyhalicyclamine A (3), have been isolated from a marine sponge Amphimedon sp. as cytotoxic constituents. Their structures were elucidated by spectroscopic analysis. Compounds 2 and 3 inhibited growth of P388 cells with IC50 values of 2.2 and 0.45 microg/mL, respectively.     

Cyclotheonamide E4 and E5, new potent tryptase inhibitors from an Ircinia species of sponge

Tryptase is a protease released from mast cells and is believed to contribute to the inflammatory process in allergic diseases including asthma. In the course of screening to find tryptase inhibitors, we isolated two new tryptase inhibitors, cyclotheonamide E4 (3) and E5 (4), from a marine sponge of the genus Ircinia. The structures of these molecules were determined by interpretation of 1H and 13C NMR spectra, and they were shown to be closely related to the previously reported cyclotheonamides E (1), E2, and E3 (2). These molecules contain two unusual amino acids, vinylogous tyrosine and alpha-ketohomoarginine, which are involved in strong activities against serine proteases. Cyclotheonamide E4 showed potent inhibitory activity against human tryptase (IC50 5.1 nM). Therefore, cyclotheonamide E4 may be useful as a therapeutic agent in the treatment of allergic diseases including asthma.     

Dictazolines A and B, bisspiroimidazolidinones from the marine sponge Smenospongia cerebriformis

An extensive study of the secondary metabolites produced by the marine sponge Smenospongia cerebriformis has led to the isolation of two new bisspiroimidazolidinone derivatives, dictazolines A (1) and B (2), along with the known soft coral metabolites tubastrindoles A (3) and B (4). The structures were assigned by 2D NMR spectroscopic methods.     

Cacofurans A and B, new furanoditerpenes from a marine sponge.

Two new labdane-class diterpenes, cacofurans A (1) and B (2), have been isolated from a sponge Cacospongia sp. Their structures were determined by analyzing spectroscopic data, by chemical transformations, and by X-ray diffraction. Cacofurans 1 and 2 inhibited the development of fertilized sea urchin eggs at concentrations of 0.5 and 5 microg/mL and showed an actin-disrupting effect on the NBT-II cell line at 10 microg/mL.     

Spongiadioxins A and B, two new polybrominated dibenzo-p-dioxins from an Australian marine sponge Dysidea dendyi.

Two new cytotoxic tetrabromodibenzo-p-dioxins, spongiadioxins A (1) and B (2), were isolated from an Australian marine sponge Dysidea dendyi. The structures of these compounds were established by 1D and 2D NMR spectroscopy, X-ray analysis of the methyl ether of spongiadioxin A (3), and synthesis of the methyl ether of spongiadioxin B (4) from diphenyl ether (9) isolated from Dysidea herbacea.     

A distinctive structural twist in the aminoimidazole alkaloids from a calcareous marine sponge: isolation and characterization of leucosolenamines A and B

Bioassay-guided fractionation of Papua New Guinea collections of Leucosolenia sp. resulted in the isolation of the novel compounds leucosolenamines A (5) and B (6) and the known compound thymidine (7). Compound 5 contains a 2-aminoimidazole core substituted at C-4 and C-5 by an N,N-dimethyl-5,6-diaminopyrimidine-2,4-dione and a benzyl group, respectively. Compound 6 retains the same core structure; however C-4 is substituted by a 5,6-diamino-1,3-dimethyl-4-(methylimino)-3,4-dihydropyrimidin-2(1H)-one moiety. This substitution pattern is unique and has never been observed in calcareous imidazole alkaloid chemistry. Leucosolenamine A (5) was mildly cytotoxic against the murine colon adenocarcinoma C-38 cell line.     

Macrophyllionium and macrophyllines A and B, oxindole alkaloids from Uncaria macrophylla

An unusual oxindole alkaloid inner salt, macrophyllionium (1), and a pair of new tetracyclic oxindole alkaloids, macrophyllines A (2) and B (3), together with six known alkaloids, were isolated from the aerial parts of Uncaria macrophylla. Corynantheidine (8) exhibited moderate cytotoxicity against HL-60 and SW480 cells with IC(50) values of 13.96 and 23.28 μM, respectively. Dihydrocorynantheine (9) exhibited significant vasodilating activity against phenylephrine-induced contraction in rat thoracic aorta rings (IC(50) = 6.73 μg/mL). In addition, compounds 2, 6, and 9 showed weak inhibitory action on KCl-induced contraction.     

Uoamines A and B, piperidine alkaloids from the ascidian Aplidium uouo

A specimen of the ascidian Aplidium uouo from Maui contained two piperidine alkaloids, uoamines A and B, that differed only in the geometry of a 3-thiomethylacrylate ester group. The alkaloids exhibit conformational mobility in the NMR time frame, which complicated the elucidation of their structures by interpretation of spectroscopic data.     

Isolation of spirastrellolides A and B from a marine sponge Epipolasis sp. and their cytotoxic activities

Spirastrellolides A (1) and B (3) have been isolated as free acids from a marine sponge Epipolasis sp. collected in the East China Sea. These compounds had been isolated from the Caribbean marine sponge Spirastrella coccinea after conversion to the methyl ester. We examined the cytotoxic activities of 1 and 3 and found that the activities of the free acids are comparable to those of the corresponding methyl esters.     

Clavosolides A and B, dimeric macrolides from the Philippines sponge Myriastra clavosa

A specimen of the sponge Myriastra clavosa from the Philippines contained two dimeric macrolides, clavosolides A and B. Clavosolide A is a symmetrical dimer, while clavosolide B is rendered unsymmetrical by the replacement of one of the methoxyl groups by a hydroxyl group. The structures of the clavosolides were elucidated by interpretation of spectroscopic data.     

Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja

A reinvestigation of Strychnos icaja roots has resulted in the isolation of two tertiary quasi-symmetric bisindole alkaloids named strychnogucines A (1) and B (2). Their structures were identified by means of spectroscopic data interpretation. Compound 2 was highly active in vitro and compound 1 moderately active against four strains of Plasmodium falciparum. Strychnogucine B (2) was more active against a chloroquine-resistant strain than against a chloroquine-sensitive one (best CI(50), 80 nM against the W2 strain). In addition, this compound showed a selective antiplasmodial activity with 25-180 times greater toxicity toward P. falciparum, relative to cultured human cancer cells (KB) or human fibroblasts (WI38).     

Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx

Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.     

Thorectandrols A and B, new cytotoxic sesterterpenes from the marine sponge Thorectandra species

Two new sesterterpenes, thorectandrol A (1) and B (2), were isolated from extracts of the marine sponge Thorectandra sp. The structures were determined by extensive NMR spectral data analysis. NOE correlations were used to define the relative stereochemistry of 1 and 2, while CD data were used to suggest their absolute stereochemistry. Both compounds 1 and 2 inhibited the growth of MALME-3M (melanoma) and MCF-7 (breast) cancer cell lines in the range 30-40 microg/mL. The known compound palauolol (3) was isolated as well and was also cytotoxic.