New apratoxins of marine cyanobacterial origin from Guam and Palau.
Two collections of the marine cyanobacterium Lyngbya sp. from Guam and Palau that both afforded the potent cytotoxin apratoxin A (1) each yielded different structural analogues with lower degrees of methylation. The new apratoxins, termed apratoxins B (2) and C (3), were evaluated for their in vitro cytotoxicity along with semisynthetic E-dehydroapratoxin A (4) to identify key structural elements responsible for the cytotoxicity and to initiate SAR studies on this novel family of depsipeptides. All analogues 2-4 displayed weaker cytotoxicity than 1, but to different extents. While compound 3 closely approached the cytotoxicity of 1, compounds 2 and 4 exhibited significantly reduced activity, possibly also related to a conformational change. The 16S rRNA genes of the different apratoxin producers have partially been sequenced and compared, and other genetic differences are currently being revealed.
Luesch
Hendrik
H
Department of Chemistry, University of Hawaii at Manoa, 96822, Honolulu, HI, USA.
Yoshida
Wesley Y
WY
Moore
Richard E
RE
Paul
Valerie J
VJ
D000595:Amino Acid Sequence; D000458:Cyanobacteria / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D047630:Depsipeptides; D006141:Guam; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009792:Oceans and Seas; D019029:Palau; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D010802:Phylogeny; D011487:Protein Conformation; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012623:Seawater / Q000382:microbiology*; D014407:Tumor Cells, Cultured
D003603:Cytotoxins; D047630:Depsipeptides; D010456:Peptides, Cyclic; D012336:RNA, Ribosomal, 16S; C470917:apratoxin B; C470919:apratoxin C; C470918:dehydroapratoxin A