Research for dinoflagellates producing cytotoxic macrolide using DNA probes and development of leads for anticancer drugs

点击翻译按钮获取中文摘要

In our searches for bioactive metabolites from marine dinoflagellates, we have isolated a series of cyototoxic macrolides, named amphidinolides, from marine symbiotic dinoflagellates Amphidinium species separated from acoel flatworms Amphiscolops species. Amphidinolides exhibit potent cytotoxicity and antitumor activity. Nevertheless, Amphidinium species with producing ability of bioactive substances such as macrolides or long-chain polyketides are difficult to discriminate acutely and conventionally by light microscopic observation. Development of the conventional method for identification and screening of Amphidinium species to produce these secondary metabolites was useful. In this study, the molecular phylogenetic investigations of Okinawan Amphidinium dinoflagellates producing bioactive secondary metabolites such as cytotoxic macrolides were examined on the basis of nuclear-encoded partial small subunit (SSU) rDNA. Furthermore, specific DNA probes were developed from 18S rDNA sequences of the Amphidinium species producing cytotoxic macrolides, and we represent the first attempt to apply molecular probes for the discrimination of dinoflagellates producing bioactive substancesDuring our continuing search for bioactive substances from marine dinoflagellates, new cytotoxic 25-membered macrolides, amphidinolide C2 have been isolated from a marine dinoflagellate Amphidinium sp.(strain Y-72). On the other hand, two new potent cytotoxic macrolides, amphidinolides B4 and B5, have been isolated from a marine dinoflagellate Amphidinium sp.(strain Y-100) separated from marine flatworm Amphiscolops sp.Solution conformation of antitumor macrolide amphidinolide H in chloroform and dimthyl sulfoxide wer investigated on the basis of NMR data.