Cylindrospermopsin, a tricyclic uracil derivative, is a cyanobacterial toxin that was first discovered in an algal bloom contaminating a local drinking supply on Palm Island in Queensland, Australia after an outbreak of a mysterious disease. Cylindrospermopsin targets protein and glutathione synthesis in hepatocytes (IC50s = 1.3 and 2.4 µM, respectively), leading to cell death. [1] It has been shown to inhibit the activity of the uridine monophosphate synthase complex with a Ki value of 10 µM.[2] Cylindrospermopsin is genotoxic, inducing DNA damage as evidenced by double strand breaks and reducing cell viability in HepG2 cells at 0.1-0.5 µg/ml.[3]
Reference:
[1]. Runnegar, M.T., Xie, C., Snider, B.B., et al. In vitro hepatotoxicity of the cyanobacterial alkaloid cylindrospermopsin and related synthetic analogues. Toxicological Sciences 67, 81-87 (2002).
[2]. Reisner, M., Carmeli, S., Werman, M., et al. The cyanobacterial toxin cylindrospermopsin inhibits pyrimidine nucleotide synthesis and alters cholesterol distribution in mice. Toxicological Sciences 82, 620-627 (2004).
[3]. Straser, A., Filipic, M., Novak, M., et al. Double strand breaks and cell-cycle arrest induced by the cyanobacterial toxin cylindrospermopsin in HepG2 cells. Mar.Drugs 11(8), 3077-3090 (2013).