New Cytotoxic Cyclic Peptide from the Marine Sponge-Associated Nocardiopsis sp. UR67

Abstract

A new cyclic hexapeptide, nocardiotide A (<b>1</b>), together with three known compounds-tryptophan (<b>2</b>), kynurenic acid (<b>3</b>), and 4-amino-3-methoxy benzoic acid (<b>4</b>)-were isolated and identified from the broth culture of <i>Nocardiopsis</i> sp. UR67 strain associated with the marine sponge <i>Callyspongia</i> sp. from the Red Sea. The structure elucidation of the isolated compounds were determined based on detailed spectroscopic data including ¹D and ²D nuclear magnetic resonance (NMR) experimental analyses in combination with high resolution electrospray ionization mass spectrometry (HR-ESI-MS), while the absolute stereochemistry of all amino acids components of nocardiotide A (<b>1</b>) was deduced using Marfey's method. Additionally, ten known metabolites were dereplicated using HR-ESI-MS analysis. Nocardiotide A (<b>1</b>) displayed significant cytotoxic effects towards the murine CT26 colon carcinoma, human HeLa cervix carcinoma, and human MM.1S multiple myeloma cell lines. The results obtained revealed sponge-associated <i>Nocardiopsis</i> as a substantial source of lead natural products with pronounced pharmacological activities.