Novel cytotoxic merocyclophanes from the cultured cyanbacterium Nostoc sp. (UIC 10110)

Cultured cyanobacteria are known to be prolific producers of biologically active natural products. Initial screening of the extract of UIC 10110, a Nostoc sp., found it to be cytotoxic against MDA-MB-435 and HT-29 cells. Dereplication by mass spectrometry and NMR indicated the presence of merocyclophane A and B [1], as well as potentially novel active constituents which were obtained using semipreparative HPLC. The complete structures of merocyclophane C and merocyclophane D were determined by a combination of 1-D and 2-D NMR experiments. The absolute stereoconfiguration of merocyclophane C and merocyclophane D was determined by CD spectroscopy. Furthermore, we investigated the influence of culture conditions on growth and chemical diversity produced by Nostoc sp. (UIC 10110). Cells were cultured in different media with different nitrate and phosphate levels following a factorial design. Metabolomics profiling by mass spectrometry and analysis using XCMS Online [2] allowed detection of secondary metabolites and relative quantification. Nitrate concentrations drastically influenced cell growth, while phosphate levels induced significant differences in the relative quantification of [7.7] paracyclophanes produced by the strain.

Acknowledgements: NCI/NIH PO1 CA125066, T32AT007533, CAPES BEX 13055 – 13 – 5.

Keywords: Cyanobacteria, Nostoc, [7.7]paracyclophanes, metabolomics.

References:

[1] Khang HS, Santarsiero BD, Kim H, Krunic A, Shen Q, Swanson SM, Chai H, Kinghorn AD, Orjala J. Merocyclophanes A and B, antiproliferative cyclophanes from the cultured terrestrial cyanobacterium Nostoc sp. Phytochemistry 2012; 79: 109 – 115

[2] Tautenhahn R, Patti GJ, Rinehart D, Siuzdak G. XCMS Online: A web-based platform to process untargeted metabolomic data, Anal Chem 2012; 84: 5035 – 5039