Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection\nof marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular\nester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered\ncompound via acyl migration at the 1,3-diol unit, and the transformation product was named\nlagunamide Dâ??. The planar structures of both compounds were elucidated using a combination of\nnuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS).\nThe absolute configurations were determined on the basis of enantioselective analysis, modified\nMosherâ??s analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure\nclosely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative\nactivity against A549 human lung adenocarcinoma cells, while the structural transformation from the\n26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide Dâ?? led to\na 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis\nin a dose- and time-dependent manner. Further investigation on the mechanism of action of the\nlagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent.
Loading....