Symplocamide A, a potent cytotoxin and chymotrypsin inhibitor from the marine Cyanobacterium Symploca sp.
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).
Linington
Roger G
RG
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Edwards
Daniel J
DJ
Shuman
Cynthia F
CF
McPhail
Kerry L
KL
Matainaho
Teatulohi
T
Gerwick
William H
WH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D000458:Cyanobacteria / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects; D008387:Marine Toxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D010219:Papua New Guinea; D010963:Plasmodium falciparum / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects
D000970:Antineoplastic Agents; D003603:Cytotoxins; D047630:Depsipeptides; D008387:Marine Toxins; C527508:symplocamide A; D002918:Chymotrypsin