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. (C) 2002 Elsevier Science Ltd. All rights reserved.