Phytochemistry: Templates for new antibacterials and 'legal highs'

Plants are exceptionally adept at producing antimicrobial and psychoactive compounds, which are presumably biosynthesized as a chemical defense strategy against fungi, bacteria and herbivory (including Man). Our work has focused on the characterization of various chemotypes that are antibacterial (e.g. 1)¹ and inhibitors of bacterial multidrug-resistance. Plants also produce phytochemicals with exquisite CNS activities from the tryptamine (N,N-dimethyl-tryptamine), tropane (cocaine) and indole (mitragynine) alkaloid, diterpene (salvinorin A), and amphetamine (cathinone, 2) classes. The last example, cathinone (2) from Khat (Catha edulis), has recently served as a template for synthetic compounds known as 'Legal Highs' or Novel Psychoactive Substances (NPS), such as mephedrone (3) and methylone (4). These compounds can be bought without legal restriction and are often strikingly similar in structure to existing controlled and harmful drugs of abuse such as ecstasy (MDMA, 5). This award lecture will broadly cover our work on plant antibacterials and NPS and discuss their potential.

References:

1. Shiu, W.K.P., et al., (2012). Journal of Natural Products 75: 336–343.

2. Gibbons, S. and Zloh, M. (2010) Bioorganic Medicinal Chemistry Letters 20: 4135–4139.