Cytotoxic bromoindole derivatives and terpenes from the Philippine marine sponge Smenospongia sp.

A detailed chemical analysis of a Philippine marine sponge Smenospongia sp. has been performed. This study yielded four new metabolites, 5-bromo-l-tryptophan (1), 5-bromoabrine (2), 5,6-dibromoabrine (3) and 5-bromoindole-3-acetic acid (4). The pyrroloiminoquinone alkaloid, makaluvamine O (5) as well as 5,6-dibromotryptamine (6), aureol (7) and furospinulosin 1 (8) were also isolated. Although 1 and 4 have been synthesized previously, this is the first report on the isolation of these compounds from a natural source. The furanosesterterpene furospinulosin 1 (8) was obtained for the first time from the genus Smenospongia. The structures of all compounds were established by spectroscopic methods (UV, IR, 1D and 2D NMR, MS, [α]D). The cytotoxic potential of 1Ð8 was evaluated in a panel of isogenic HCT-116 human colon tumor cell lines

Bisabolane type sesquiterpenes from a marine Didiscus sponge

Two bisabolane type sesquiterpene phenols, (+)-curcuphenol (1) and (+)-curcudiol (2), were isolated from a Philippine marine sponge, Didiscus sp., in addition to b -sitosterol (3) and phenethylamine (4). The structures of the metabolites were established on the basis of spectral evidence (1D- and 2D NMR, [a]D, EIMS). (+)-Curcuphenol (1) showed cytotoxicity, which is indicative of a p53 independent mechanism

Attenuation of Age-Related Metabolic Dysfunction in Mice With a Targeted Disruption of the Cβ Subunit of Protein Kinase A

The cyclic adenosine monophosphate–dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cβ. We confirmed that Cβ has high levels of expression in the brain but also showed moderate levels in liver. Cβ-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cβ protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance

New terpenoids from a Cacospongia sp from the Philippines

Four new terpenoids, cacospongins A (1), B (2), C (3) and D (4), have been isolated from the Philippine sponge Cacospongia sp. Also isolated were 15,16-epoxy-8(17),13(16),14-labdatriene (5), ambliofuran (6) and luffariellolide (7). The structures of compounds 1-7 were determined by means of spectroscopic evidence

Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1)

Raf/MEK-1/MAPK cascade inhibitor activity-directed fractionation of the sponge Stylissa massa afforded eight known alkaloids:  aldisine (1), 2-bromoaldisine (2), 10Z-debromohymenialdisine (3), 10E-hymenialdisine (4), 10Z-hymenialdisine (5), hymenin (6), oroidin (7), and 4,5-dibromopyrrole-2-carbonamide (8). Both 4 and 5 showed significant enzyme inhibitory activity (IC50 3 and 6 nM, respectively). Secondary assays identified these compounds as potent MEK-1 inhibitors. Compounds 4 and 5 also inhibited the growth of human tumor LoVo cells

Bioactive isomalabaricane triterpenes from the marine sponge Rhabdastrella globostellata

Two new isomalabaricane triterpenes, stellettin H (1) and stellettin I (2), have been isolated from the marine sponge Rhabdastrella globostellata, collected from the Philippines. Stellettins A−D (3−6), (−)-stellettin E (7), and rhabdastrellic acid-A (8) were also isolated and characterized. Stellettin B (4) and (−)-stellettin E (7) showed selective cytotoxicity toward p21WAF1/Cip1-deficient human colon tumor (HCT-116) cells with IC50 values of 0.043 and 0.039 μM, respectively

Platelet aggregation inhibitors from Philippine marine invertebrate samples screened in a new microplate assay

A new microplate assay for Ca(2+)-induced platelet aggregation as detected by Giemsa dye was used to screen marine invertebrate samples from the Philippines for inhibitors of human platelet aggregation. Out of 261 crude methanol extracts of marine sponges and tunicates, 25 inhibited aggregation at 2 mg/ml. Inhibition of agonist-induced aggregation in an aggregometer was used to confirm results of the microplate assay and to determine the specific mode of inhibition of 2 samples. The marine sponge Xestospongia sp. yielded a xestospongin/araguspongine-type molecule that inhibited collagen-induced aggregation by 87% at 2 micro g/ml, and epinephrine-induced aggregation by 78% at 20 micro g/ml, while the marine sponge Aplysina sp. yielded 5,6-dibromotryptamine, which inhibited epinephrine-induced aggregation by 51% at 20 micro g/ml. In this study we have found that the microplate assay is a simple, inexpensive, yet useful preliminary tool to qualitatively screen a large number of marine samples for antiplatelet aggregation activity

Microcionamides A and B, bioactive peptides from the Philippine sponge Clathria (Thalysias) abietina

Microcionamides A (1) and B (2) have been isolated from the Philippine marine sponge Clathria (Thalysias) abietina. These new linear peptides are cyclized via a cystine moiety and have their C-terminus blocked by a 2-phenylethylenamine group. Their total structures, including absolute stereochemistry, were determined by a combination of spectral and chemical methods. Compound 1 was shown to slowly isomerize about the C-36/C-37 double bond when stored in DMSO. Microcionamides A (1) and B (2) exhibited significant cytotoxicity against the human breast tumor cells lines MCF-7 and SKBR-3 and displayed inhibitory activity against Mycobacterium tuberculosis H37Ra