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]
5-Chlorouracil is a chlorinated derivative of the pyrimidine nucleoside base uracil . In vivo, it is converted into chlorodeoxyuridine, which is mutagenic and genotoxic.1 Uracil is chlorinated at the 5 position in a cell-free myeloperoxidase, peroxide, and chloride system in which hypochlorous acid is formed.2 5-Chlorouracil has been found in human neutrophils stimulated with phorbol 12-myristate 13-acetate in vitro and in inflammatory human exudate isolated from sites of superficial infection. Levels of 5-chlorouracil are increased in exudate isolated from the site of inflammation in a rat model of carrageenan-induced inflammation and in patient-derived human atherosclerotic aortic tissue.3,4References 5-Chlorouracil is a chlorinated derivative of the pyrimidine nucleoside base uracil . In vivo, it is converted into chlorodeoxyuridine, which is mutagenic and genotoxic.1 Uracil is chlorinated at the 5 position in a cell-free myeloperoxidase, peroxide, and chloride system in which hypochlorous acid is formed.2 5-Chlorouracil has been found in human neutrophils stimulated with phorbol 12-myristate 13-acetate in vitro and in inflammatory human exudate isolated from sites of superficial infection. Levels of 5-chlorouracil are increased in exudate isolated from the site of inflammation in a rat model of carrageenan-induced inflammation and in patient-derived human atherosclerotic aortic tissue.3,4 References
Arecaidine propargyl ester is an agonist of M2muscarinic acetylcholine receptors (mAChRs).1It selectively binds to M2over M1, M3, M4, and M5mAChRs in CHO cells expressing the human receptors (Kis = 0.0871, 1.23, 0.851, 0.977, and 0.933 μM, respectively). Arecaidine propargyl ester induces contractions in isolated guinea pig atrium (pD2= 8.67). It induces apoptosis and the production of reactive oxygen species (ROS) in U87 and U251 glioblastoma cells when used at a concentration of 100 μM.2Arecaidine propargyl ester decreases mean arterial blood pressure in normotensive cats (ED25= 1.9 nmol kg).3It is toxic to house flies (Musca) when administered at a dose of 75 μg fly.4 1.Scapecchi, S., Matucci, R., Bellucci, C., et al.Highly chiral muscarinic ligands: the discovery of (2S,2’R,3’S,5’R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonistJ. Med. Chem.49(6)1925-1931(2006) 2.Di Bari, M., Tombolillo, B., Conte, C., et al.Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cellsNeurochem. Int.90261-270(2015) 3.Porsius, A.J., and Van Zwieten, P.A.Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of catsProg. Brain Res.47131-135(1977) 4.Honda, H., Tomizawa, M., and Casida, J.E.Insect muscarinic acetylcholine receptor: Pharmacological and toxicological profiles of antagonists and agonistsJ. Agric. Food Chem.55(6)2276-2281(2007)
Cyanazine, a triazine herbicide, is utilized for effective control of a diverse range of grass and broadleaf weeds. It has been scientifically validated as non-genotoxic.