Isolation of Antiproliferative Natural Products from Cyanobacteria

Cyanobacteria are Gram-negative photosynthetic bacteria with diverse biosynthetic pathways that produce secondary metabolites with unique chemical scaffolds and biological activities. In this work, we describe the usage of high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and bioassay-guided isolation techniques to purify and identify novel metabolites from cultured cyanobacteria Oscillatoria sp. UIC 11063 and Nostoc sp. UIC 11044. We report the dereplication of nostopeptolide A1/A2, a known cyclic depsipeptide, from Nostoc sp. UIC 11044. We also describe the dereplication of calothrixin B and the isolation of N-methyl-calothrixin B, a novel natural product from cyanobacterium Oscillatoria sp. UIC 11063. N-methyl-calothrixin B and calothrixin B were isolated via reverse-phase semi-preparative HPLC and structures were elucidated using HRMS and 1D/2D NMR. These compounds were additionally evaluated for their anti-proliferative activities in human ovarian cancer (OVCAR3) and human melanoma cancer cell (MDA-MB-435) lines, where calothrixin B showed significant anti-proliferative activity.