Homesteadamides A - H, antiproliferative cyclic lipodecapeptides from the cultured freshwater cyanobacterium cf. Anabaena sp. (UIC 10035)

Abstract

Cyanobacteria are one of the well-known producers of lipopeptides. The UIC 10035 strain was obtained from the sample collected near the town of Homestead, south Florida, and designated as Cf. Anabaena sp. based on morphological and 16S rRNA gene sequence analyses. The extract of the cultured strain UIC 10035 showed an antiproliferative activity against MDA-MB-435 cells. Bioassay-guided fractionation of the extract led to the isolation of a series of lipopeptides, named homesteadamides A – H. The planar structures were determined by analysis of HRESIMS, tandem MS, and 1D and 2D NMR data. The stereoconfigurations were assigned by LC-MS analysis of the Marfey's derivatives after acid hydrolysis. Homesteadamides A – H exhibited antiproliferative activity against MDA-MB-435 cells with low micromolar IC50 values ranging between 1 and 10 µM. The structures of homestedamides A – H are characterized by the presence of a lipophilic β-amino acid and three non-standard amino acids NMeAsn, OMeThr and Dhb (α,β-dehydro-α-aminobutyric acid).