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  • Title: From Weed Killer to Wonder Drug.
    Author: Lock EA.
    Journal: Adv Exp Med Biol; 2017; 959():175-185. PubMed ID: 28755195.
    Abstract:
    The discovery that a natural product leptospermone had herbicidal activity formed the starting point for chemical synthesis to find more activity and selectivity. A series of molecules called triketones were found to possess good activity and 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) was selected for toxicology testing. NTBC fed at low doses to rats and dogs caused keratopathy, which on cessation of the diet recovered. Mice, rabbits and monkeys fed NTBC did not show this response. Research discovered that NTBC caused tyrosinaemia which was due to inhibition of the enzyme 4-hydroxyphenylpyruvate dioxygenase in both mammals and plants thereby finding a novel target for killing plants. NTBC was also used sucessfully as a drug to treat a rare inborn error of metabolism, tyrosinaemia type I, in collaboration with Professor's Sven Lindstedt and Elisabeth Holme. Understanding the mechanism of toxicity of NTBC led to novel herbicide discovery and saved the lives of children with acute tyrosinaemia type I.
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