As part of the Panama International Cooperative Biodiversity Groups (ICBG) project, two new (2, 4) and two known (1, 3) linear alkynoic lipopeptides have been isolated from a Panamanian strain of the marine cyanobacterium Lyngbya majuscula. Carmabin A (1), dragomabin (2), and dragonamide A (3) showed good antimalarial activity (IC 50 4.3, 6.0, and 7.7 μM, respectively) whereas the non-aromatic analog, dragonamide B (4), was inactive. The planar structures of all four compounds were determined by NMR spectroscopy in combination with mass spectrometry, and their stereoconfigurations were established by chiral HPLC and by comparison of their optical rotations and NMR data with literature values.Artemisinin Combination Treatments (ACTs) for falciparum malaria are currently the only first-line antimalarial drugs amenable to widespread use against all chloroquine-resistant malaria parasites. 1 However, their effective distribution to combat malaria in economically disadvantaged regions could require an annual global subsidy of $300-500 million. 2 Furthermore, in the event of successful widespread use of the artemisinins, the development of resistance to these drugs before effective replacements or alternatives are at hand is a cause for profound concern. Therefore, the development of new classes of antimalarial drugs remains an enormous challenge and is a focus of many collaborative research efforts, including the International Cooperative Biodiversity Groups project in Panama, which investigates Panamanian terrestrial plants, endophytes and marine organisms as sources of tropical disease treatments. 3 As part of this program, we have been investigating marine cyanobacteria as a source of antimalarial agents, and found that the organic extracts of a red Panamanian strain of the marine cyanobacterium Lyngbya majuscula were active against chloroquine-resistant Plasmodium falciparum. To the best of our knowledge, there are only three reports of marine cyanobacterial metabolites isolated with antimalarial activity. Most recently, members of our * To whom correspondence should be addressed. Tel: 541 737 5808. Fax: 541 737 3999. E-mail: kerry.mcphail@oregonstate.edu. Supporting Information Available: 1 H and 13 C NMR spectra in CDCl 3 for carmabin A (1), dragomabin (2), dragonamide A (3) and dragonamide B (4). Results and DiscussionThe organic extracts of two collections of L. majuscula from different sites in Bocas del Toro, Panama (2002 and2003) showed significant activity against chloroquine-resistant Plasmodium falciparum (IC 50 = 6 and 26 μg/mL). Crude fractionation by normal-phase vacuum-liquid chromatography (NP-VLC) of the most active collection from Isla Bastimentos (Bocas del Toro, 2002) produced two relatively polar fractions (100% EtOAc and 25% MeOH-EtOAc) with good antimalarial activity (<2 and 1 μg/mL, respectively). Solid-phase extraction (SPE) and reversed-phase HPLC of the 25% MeOH-EtOAc NP-VLC fraction yielded carmabin A (1) and dragomabin (2) as the active components.Structure elucidation of li...

No abstract

The marine-derived filamentous fungus Asteromyces cruciatus 763, obtained off the coast of La Jolla, San Diego, USA, yielded the new pentapeptide lajollamide A (1), along with the known compounds regiolone (2), hyalodendrin (3), gliovictin (4), 1N-norgliovicitin (5), and bis-N-norgliovictin (6). The planar structure of lajollamide A (1) was determined by Nuclear Magnetic Resonance (NMR) spectroscopy in combination with mass spectrometry. The absolute configuration of lajollamide A (1) was unambiguously solved by total synthesis which provided three additional diastereomers of 1 and also revealed that an unexpected acid-mediated partial racemization (2:1) of the L-leucine and L-N-Me-leucine residues occurred during the chemical degradation process. The biological activities of the isolated metabolites, in particular their antimicrobial properties, were investigated in a series of assay systems.