2-pyrones possessing antimicrobial and cytotoxic activities.
The 2-pyrone sub-unit is found in a number of natural products possessing broad spectrum biological activity. Such compounds are validated as being capable of binding to specific protein domains and able to exert a remarkable range of biological effects. In an effort to identify synthetic 2-pyrones with interesting biological effects, herein we report the synthesis and biological evaluation of 4-substituted-6-methyl-2-pyrones. Synthetic routes to 4-alkyl/alkenyl/aryl/alkynyl-6-methyl-2-pyrones have been developed utilising Sonogashira, Suzuki and Negishi cross-coupling starting from readily available 4-bromo-6-methyl-2-pyrone. Specific conditions for each organometallic protocol were required for successful cross-coupling. In particular, a triethylamine/acetonitrile--base/solvent mixture was crucial to Sonogashira alkynylation of 4-bromo-6-methyl-2-pyrone, whereas thallium carbonate was a mandatory base for the Suzuki cross-coupling of trialkylboranes. The 2-pyrones demonstrate potent inhibitory activity against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Schizosaccharomyces pombe and Botrytis cinerea. The growth inhibitory activities of selected 2-pyrones were determined in A2780 human ovarian carcinoma and K562 human chronic myelogenous leukaemia cell lines using an in vitro cell culture system (MTT assay). These studies demonstrate that 4-phenylethynyl-, 4-tetrahydropyranylpropargyl ether- and 4-ethynyl-6-methyl-2-pyrones have excellent potential as a new class of anticancer agents.
Fairlamb IJ, Marrison LR, Dickinson JM, Lu FJ, Schmidt JP