Synthesis and antimicrobial evaluation of farnesyl diphosphate mimetics.
The synthesis and first antimicrobial evaluation of farnesyl diphosphate mimetics are described. Several analogues (10, 12, 13, and 20) are inhibitors of Candida albicans, Shizosaccharomyces pombe, and Saccharomyces cerevisiae. The activities of analogues 10, 12, and 13, which contain a omega-phenyl moiety and a diphosphate isostere, are not attributable to inhibition of sterol biosynthesis via squalene synthase. Two geranyl phenylsulphones (14 and 15) are potent inhibitors of Escherichia coli. Analogue 15 exhibits potent activity towards Salmonella typhimurium and Pseudomonas aeruginosa (MIC-2 microg/mL) and represents the first type of semi-synthetic terpenoid allylic sulphone active against these bacteria.
Fairlamb
Ian J S
IJ
Department of Chemistry and Materials, John Dalton Building, The Manchester Metropolitan University, Chester Street, Manchester M20 5GD, UK. ijsf1@york.ac.uk
Dickinson
Julia M
JM
O'Connor
Rachael
R
Cohen
Louis H
LH
van Thiel
Christa F
CF
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000166:cytology / Q000187:drug effects*; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000494:pharmacology*; D012717:Sesquiterpenes; D013045:Species Specificity; D015003:Yeasts / Q000166:cytology / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate