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
Ian J S
IJ
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK. ijsf@york.ac.uk
Marrison
Lester R
LR
Dickinson
Julia M
JM
Lu
Feng-Ju
FJ
Schmidt
Jan Peter
JP
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011753:Pyrones