ABSTRACT
Palmerolides D-G are new bioactive macrolides isolated from the Antarctic tunicate Synoicum adareanum and are related to the melanoma-selective cytotoxin palmerolide A. Most of these palmerolides are potent V-ATPase inhibitors and have sub-micromolar activity against melanoma. Though palmerolide A remains the most potent of this series of natural products against mammalian V-ATPase, recent data suggests that palmerolide D is the most potent against melanoma. A comparison of the bioactivity data obtained for these natural product palmerolides has provided insight into the substructures necessary to retain V-ATPase inhibition and cytotoxic activity.
Subject(s)
Macrolides/chemistry , Urochordata/chemistry , Animals , Antarctic Regions , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cattle , Humans , Macrolides/isolation & purification , Macrolides/pharmacology , Melanoma/drug therapy , Molecular Conformation , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , Vacuolar Proton-Translocating ATPases/antagonists & inhibitorsABSTRACT
Chemical investigation of five Antarctic macroalgae whose tissues and crude extracts displayed ecologically relevant feeding deterrence in field bioassays was performed. Eleven compounds were characterized from the three red algae studied, of which four (1-3 and 9) were previously unreported, and four compounds were found from two brown algae, two (12 and 14) of which are new natural products. Several of these pure compounds have been individually investigated in ecological and/or pharmacological bioassays.