Synthesis and antimicrobial evaluation of farnesyl diphosphate mimetics
article
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 ω-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 - 2μg/mL) and represents the first type of semi-synthetic terpenoid allylic sulphone active against these bacteria. © 2003 Elsevier Science (USA). All rights reserved. Chemicals/CAS: farnesyl diphosphate, 13058-04-3, 372-97-4; squalene synthase, 9077-14-9; Anti-Bacterial Agents; Antifungal Agents; farnesyl pyrophosphate, 13058-04-3; Polyisoprenyl Phosphates
Topics
Antimicrobial agentsCopper(I) catalysed tetrahydropyranyl ether displacementsFarnesyl-protein transferaseInhibitorsSqualene synthase10 phenyl 5,9 dimethyldecadienoic acid2 (diethoxyphosphinyl) 10 phenyl 5,9 dimethyldecadienoic acid2 phosphono 10 phenyl 5,9 dimethyldecadienoic acid3,7 dimethyloctadien 1 phenylsulfone8 benzoxy 3,7 dimethyloctadien 1 ol8 hydroxy 3,7 dimethyloctadien 1 phenylsulfoneantiinfective agentfarnesyl diphosphatefunctional groupsqualene synthaseunclassified drugantimicrobial activitybrominationCandida albicanscontrolled studydrug inhibitiondrug mechanismdrug potencydrug screeningdrug synthesisnonhumanoxidationSaccharomyces cerevisiaesterol synthesisstructure analysisAnti-Bacterial AgentsAntifungal AgentsBacteriaBiomimetic MaterialsCell DivisionPolyisoprenyl PhosphatesSpecies SpecificityYeastsCandida albicansEscherichia coliPseudomonasPseudomonas aeruginosaSaccharomyces cerevisiaeSalmonella typhimuriumTyphimurium
TNO Identifier
236945
ISSN
00452068
Source
Bioorganic Chemistry, 31(1), pp. 80-97.
Pages
80-97
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