Malyngolide Dimer, a Bioactive Symmetric Cyclodepside from the Panamanian Marine Cyanobacterium Lyngbya majuscula

• Published in: Journal of natural products (Washington, D.C.) Vol. 73; no. 4; pp. 709 - 711
• Main Authors: Gutiérrez, Marcelino, Tidgewell, Kevin, Capson, Todd L, Engene, Niclas, Almanza, Alejandro, Schemies, Jörg, Jung, Manfred, Gerwick, William H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 23.04.2010; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Biological and medical sciences; Chemistry, Medicinal; Chloroquine - pharmacology; Cyanobacteria - chemistry; Drug Resistance - drug effects; Ethers, Cyclic - chemistry; Ethers, Cyclic - isolation & purification; Ethers, Cyclic - pharmacology; Fundamental and applied biological sciences. Psychology; General aspects; Humans; Lactones - chemistry; Lactones - isolation & purification; Life Sciences & Biomedicine; Lyngbya Toxins - chemistry; Lyngbya Toxins - isolation & purification; Lyngbya Toxins - pharmacology; Marine Biology; Microbiology; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Panama; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Plant Sciences; Plasmodium falciparum - drug effects; Pyrones - chemistry; Pyrones - isolation & purification; Pyrones - pharmacology; Science & Technology; Structure-Activity Relationship; Central America; Panama; America; ASSAYS; TANIKOLIDE; Antineoplastic agent; Antimalarial; Lung; Cytotoxicity; Macrocycle; Marine environment; Antiprotozoal agent; Plasmodium falciparum; Cyanobacteria; Bacteria; Tumor cell; Non small cell carcinoma; Human; Protozoa; Apicomplexa; Lactone; Biological activity; Cell line; Microbial origin; Absolute configuration; Parasiticide; Isolation; Active ingredient; Dimer; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np9005184

Fractionation of the extract of the marine cyanobacterium Lyngbya majuscula collected from Panama led to the isolation of malyngolide dimer (1). The planar structure of 1 was determined using 1D and 2D NMR spectroscopy and HRESI-TOFMS. The absolute configuration was established by chemical degradation followed by chiral GC-MS analyses and comparisons with an authentic sample of malyngolide seco-acid (4). Compound 1 showed moderate in vitro antimalarial activity against chloroquine-resistant Plasmodium falciparum (W2) (IC50 = 19 μM) but roughly equivalent toxicity against H-460 human lung cell lines. Furthermore, because the closely related cyanobacterial natural product tanikolide dimer (5) was a potent SIRT2 inhibitor, compound 1 was evaluated in this assay but found to be essentially inactive.