Norselic acids A-E, highly oxidized anti-infective steroids that deter mesograzer predation, from the Antarctic sponge Crella sp.

Five new steroids, norselic acids A-E (1-5), were isolated from the sponge Crella sp. collected in Antarctica. The planar structures of the norselic acids were established by extensive NMR spectroscopy and mass spectrometry studies, and the configuration of norselic acid A (1) was elucidated by X-ray crystallography. Norselic acid A displays antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), vancomycin-resistant Enterococcus faecium (VRE), and Candida albicans and reduces consumption of food pellets by sympatric mesograzers. Compounds 1-5 are also active against the Leishmania parasite at low micromolar levels.

Isolation of three new naturally occurring compounds from the culture of Micromonospora sp. P1068.

Bioassay guided isolation of an antibacterial extract prepared from the fermentation broth of a Micromonospora sp. P1068 led to the isolation of eight compounds identified as (3R) 3,4',7-trihydroxy-isoflavanone (1), 3-hydroxydehydrodaidzein, daidzein (2), 3-methyl-1H-indole-2-carboxylic acid (3), 1H-indole-3-carboxaldehyde (4), 3-(p-hydroxyphenyl)-N-methylpropionamide, N-methylphloretamide (5), phenyl acetic acid (6), 2-hydroxy phenyl acetic acid (7) and 4-hydroxy-5-methoxy-benzoic acid (8). Compounds 1 and 5 were found to be novel chemical entities while 3 was isolated from a natural source for the first time. All compounds were evaluated for their antimicrobial activities against a panel of clinically significant microorganisms. Compound 4 was active against Staphylococcus aureus (MIC, 32 microg/ml), Enterococcus faecium (MIC, 32 microg/ml) and Escherichia coli (MIC, 64 microg/ml).

Chemical investigation of predator-deterred macroalgae from the Antarctic peninsula.

Chemical investigation of five Antarctic macroalgae whose tissues and crude extracts displayed ecologically relevant feeding deterrence in field bioassays was performed. Eleven compounds were characterized from the three red algae studied, of which four (1-3 and 9) were previously unreported, and four compounds were found from two brown algae, two (12 and 14) of which are new natural products. Several of these pure compounds have been individually investigated in ecological and/or pharmacological bioassays.

Dictyosphaeric acids A and B: new decalactones from an undescribed Penicillium sp. obtained from the alga Dictyosphaeria versluyii.

Fungal isolate F01V25 was obtained from the alga Dictyosphaeria versluyii collected near Dravuni, Fiji, in 2001 and represented a previously undescribed Penicillium sp. Fermentation of isolate F01V25 resulted in the production of two new polyketides, dictyosphaeric acids A and B, along with the known anthraquinone carviolin. The relative stereochemistry of dictyosphaeric acids A and B was determined using the J-based configuration analysis method in conjunction with ROE and NOE correlations.

Constituents of antibacterial extract of Caesalpinia paraguariensis Burk.

The Argentinean legume Caesalpinia paraguariensis Burk. (Fabaceae) was selected for further fractionation work based on the strong antimicrobial activity of its CH2Cl2-MeOH (1:1 v/v) extract against a host of clinically significant microorganisms, including antibiotic resistant strains. 1D and 2D NMR enabled the identification of the novel benzoxecin derivative caesalpinol along with the known compounds bilobetin, stigma-5-en-3-O-beta-6'-stearoylglucopyranoside, stigma-5-en-3-beta-6'-palmitoylglucopyranoside, stigma-5-en-3-beta-glucopyranoside, oleanolic acid, 3-O-(E)-hydroxycinnamoyl oleanolic acid, betulinic acid, 3-O-(E)-hydroxycinnamoyl betulinic acid, and lupeol from the active fractions. Oleanolic acid was found active against Bacillus subtilis and both methicillin-sensitive and -resistant Staphylococcus aureus with MICs of 8 (17.5 microM), 8 and 64 (140 microM) microg/ml, respectively. The rest of the compounds, however, did not show activity.

Brocaenols A-C: novel polyketides from a marine derived Penicillium brocae.

Chemical investigation of a Penicillium brocae, obtained from a tissue sample of a Fijian Zyzyya sp. sponge, yielded two known diketopiperazines and three novel cytotoxic polyketides, brocaenols A-C. The brocaenols contain an unusual enolized oxepine lactone ring system that to the best of our knowledge is unprecedented in the literature. The structures were elucidated by using 2D-NMR methods including an INADEQUATE experiment. The absolute stereochemistry of brocaenol A was established by using a modified Mosher method. The taxonomy of the producing fungus was elucidated by using both morphological and rDNA sequence analysis.

Antibacterial diterpenes from Calceolaria pinifolia.

Two new isopimaranes, 19-methylmalonyloxy-ent-isopimara-8(9),15-diene (5) and 19-malonyloxy-ent-isopimara-8(9),15-diene (6), were isolated using bioassay-guided fractionation of the CH(2)Cl(2)-MeOH (1:1) extract of the aerial part of Calceolaria pinifolia along with eight other diterpenes (1-4, 7-10) and two triterpenes (11, 12). All compounds were assayed against Staphylococcus aureus (SA), methicillin-resistant S. aureus (MRSA), Bacillus subtilis (BS), and Escherichia coli (EC). 4-Epi-dehydroabietinol (2) and ent-isopimara-9(11),15-diene-19-ol (8) were found to be active against MRSA with MIC values of 8 and 2 microgram/mL, respectively. Mechanistic studies of 8 in BS suggested rapid and nonspecific inhibition of uptake and incorporation of radiolabeled precursors into DNA, RNA, and protein consistent with membrane-damaging effects in bacteria. Compound 8 did not afford protection against an acute infection with SA in mice.

New antimicrobial cycloartane triterpenes from Acalypha communis.

Three new cycloartane-type triterpenes, 16 alpha-hydroxymollic (1), 15 alpha-hydroxymollic (2), and 7 beta,16 beta-dihydroxy-1,23-dideoxyjessic acids (3), were isolated from the aerial parts of Acalypha communis. The structures of the novel triterpenes were determined by spectroscopic methods as well as chemical derivatization. These compounds were tested for their antimicrobial activity against Gram-positive and -negative bacteria. Compounds 1-3 exhibited moderate antimicrobial activity (MIC 8, 32, 8 microg/mL, respectively) against vancomycin-resistant enterococci. In addition, compound 1 was found to be active against methicillin-resistant staphylococci. In contrast, compounds 1-3 were poorly active against Gram-negative bacteria. Compound 3 was tested in an in vivo model; it did not provide protection to mice infected with Staphylococcus aureus.