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.
References
- Kobayashi, J. Amphidinolides and its related macrolides from marine dinoflagellates. J. Antibiot. 2008, 61, 271. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, J.; Kubota, T. Bioactive macrolides and polyketides from marine dinoflagellates of the genus amphidinium. J. Nat. Prod. 2007, 70, 451. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, J.; Tsuda, M. Amphidinolides, bioactive macrolides from symbiotic marine dinoflagellates. Nat. Prod. Rep. 2004, 21, 77. [Google Scholar] [CrossRef] [PubMed]
- Tsuda, M.; Kumagai, K.; Masuda, A.; Fukushi, E.; Kawabata, J. Iriomoteolide-2a, a Cytotoxic 23-membered macrolide from marine benthic dinoflagellate Amphidinium species. Heterocycles 2015, 91, 265. [Google Scholar] [CrossRef]
- Rodríguez-Escrich, C.; Urpí, F.; Vilarrasa, J. Stereocontrolled total synthesis of amphidinolide X via a silicon-tethered metathesis reaction. Org. Lett. 2008, 10, 5191. [Google Scholar] [CrossRef] [PubMed]
- Trigili, C.; Pera, B.; Barbazanges, M.; Cossy, J.; Meyer, C.; Pineda, O.; Rodríguez-Escrich, C.; Urpí, F.; Vilarrasa, J.; Díaz, J.F.; et al. Mechanism of action of the cytotoxic macrolides anphidinolide X and J. ChemBioChem 2011, 12, 1027. [Google Scholar] [CrossRef] [PubMed]
- Mola, L.; Olivella, A.; Urpí, F.; Vilarrasa, J. Synthesis of amphidinolide Y precursors. Tetrahedron Lett. 2014, 55, 900. [Google Scholar] [CrossRef]
- Sánchez, D.; Andreou, T.; Costa, A.M.; Meyer, K.G.; Williams, D.R.; Barasoain, I.; Díaz, J.F.; Lucena-Agell, D.; Vilarrasa, J. Total synthesis of amphidinolide K, a macrolide that stabilizes F-Actin. J. Org. Chem. 2015, 80, 8511. [Google Scholar] [CrossRef] [PubMed]
- Bosch, L.; Mola, L.; Petit, E.; Saladrigas, M.; Esteban, J.; Costa, A.M.; Vilarrasa, J. Formal total synthesis of amphidinolide E. J. Org. Chem. 2017, 82, 11021. [Google Scholar] [CrossRef] [PubMed]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).