Symplocamide A, a Potent Cytotoxin and Chymotrypsin Inhibitor from the Marine Cyanobacterium Symploca sp

• Published in: Journal of natural products (Washington, D.C.) Vol. 71; no. 1; pp. 22 - 27
• Main Authors: Linington, Roger G, Edwards, Daniel J, Shuman, Cynthia F, McPhail, Kerry L, Matainaho, Teatulohi, Gerwick, William H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 01.01.2008; Amer Chemical Soc; American Society of Pharmacognosy; American Chemical Society
• Subjects: Animals; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; anticarcinogenic activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Applied microbiology; Biological and medical sciences; chemical structure; Chemistry, Medicinal; Chemotherapic agents; chymotrypsin; Chymotrypsin - antagonists & inhibitors; cultured cells; Cyanobacteria; Cyanobacteria - chemistry; Cyanophyta; cytotoxicity; cytotoxins; Cytotoxins - chemistry; Cytotoxins - isolation & purification; Cytotoxins - pharmacology; depsipeptides; Depsipeptides - chemistry; Depsipeptides - isolation & purification; Depsipeptides - pharmacology; Drug Screening Assays, Antitumor; enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Leishmania donovani - drug effects; Life Sciences & Biomedicine; Marine Toxins - chemistry; Marine Toxins - isolation & purification; Marine Toxins - pharmacology; Microbiology; Molecular Structure; Papua New Guinea; Pharmacology & Pharmacy; Plant Sciences; Plasmodium falciparum - drug effects; Science & Technology; spectral analysis; stereochemistry; Symploca; symplocamide; Trypanosoma cruzi - drug effects; Papua New Guinea; Melanesia; Oceania; PEPTIDES; BARBAMIDE BIOSYNTHESIS; OSCILLATORIA-AGARDHII; ANALOG; ELASTASE; MICROCYSTIS-AERUGINOSA NIES-88; WATER BLOOM; PLASMIN; PROTEASE INHIBITORS; Antineoplastic agent; Oligopeptides; Cyclic peptides; Lung; Cytotoxicity; Selectivity; Neuroblastoma; Marine environment; Cyanobacteria; Bacteria; Tumor cell; Non small cell carcinoma; Human; Serine endopeptidases; Enzyme; Enzyme inhibitor; In vitro; Biological activity; Peptidases; Chymotrypsin; Cell line; Microbial origin; Depsipeptide; Hydrolases; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np070280x

Investigation of a Symploca sp. from Papua New Guinea has led to the isolation of symplocamide A (1), a potent cancer cell cytotoxin, which also inhibits serine proteases with a 200-fold greater inhibition of chymotrypsin over trypsin. The complete stereostructure of symplocamide A was determined by detailed NMR and MS analysis as well as chiral HPLC analysis of the component amino acid residues. The presence of several unusual structural features in symplocamide A provides new insights into the pharmacophore model for protease selectivity in this drug class and may underlie the potent cytotoxicity of this compound to H-460 lung cancer cells (IC50 = 40 nM) as well as neuro-2a neuroblastoma cells (IC50 = 29 nM).