海洋生物からの医薬シーズの探索

Abstract

In search of new pharmaceutically valuable substances from marine organisms, we have been engaged in chemical studies 1] structural elucidation; 2] asymmetric total synthesis; 3] elucidation of pharmacophore by analysis of structure–activity relationship; 4] action mechanism and search for target protein on the bioactive substances, which were isolated from marine invertebrates and marine microorganisms at Japanese coasts and Indonesian coral reefs on the guidance of new practical bioassay. a) Anti–angiogenic substance: selective growth–inhibitor against human umbilical vein endothelial cells (HUVECs) (e.g. cortistatin A: 9(10–19)–abeo–androstane–type steroidal alkaloid having isoquinoline unit) b) Hypoxia–selective growth inhibitor: growth inhibitor against tumor cells under hypoxic environment selectively (e.g. furospinosulin–1: furanosesterterpene) c) Anti–mycobacterial substances, which are effective to both active and non–replicating persistent (NRP) states of tuberculosis (e.g. halicyclamine A: macrocyclic alkaloid)