Amphidinolides and Iriomoteolides, Potent Anticancer Macrolides ^†

Amphidinolides and iriomoteolides are complex macrolides isolated from cultured marine dinoflagellates of the genus Amphidinium sp. [1,2,3,4]. All of them are cytotoxic against several cancer cell lines, especially those with larger rings, with activities in the nanomolar range. Some years ago, we started a research program directed towards the synthesis and elucidation of the biological mechanism of action of several members of this family of natural products [5,6,7,8,9]. As part of this research effort, we have completed the total synthesis of some amphidinolides. Work is underway in our laboratories to complete the total synthesis of amphidinolide B₂ and iriomoteolide 2a.

Amphidinolide K and some of its stereoisomers and analogues were subjected to evaluation of the possible disruption of the α,β-tubulin–microtubule and/or G-actin–F-actin equilibria. Preliminary studies suggest that amphidinolide K behaves as a stabilizer of F-actin in vitro. The interaction of several of these macrolides with actin has also been studied computationally in our laboratories.