RRC ID 46945
Author Uesono Y, Toh-E A, Kikuchi Y, Terashima I.
Title Structural analysis of compounds with actions similar to local anesthetics and antipsychotic phenothiazines in yeast.
Journal Yeast
Abstract Local anesthetics and antipsychotic phenothiazines cause a rapid shutdown of both actin polarization and translation initiation in yeast cells, like some environmental stresses. These compounds all have an amphiphilic structure, surfactant activity and the ability to lyse yeast cells. To elucidate the structures responsible for the shutdown activity and cell lysis, we investigated a variety of amphiphiles. In the hydrophobic region, the straight alkyl structure was sufficient for the shutdown of actin polarization and translational initiation. In the hydrophilic region of the straight alkyl compounds, cationic trimethyl ammonium (TMA) and non-ionic hydroxyl structure (alcohols) shut down both reactions, while an anionic structure, sulphate, with a long alkyl chain (≥C6) shut down actin polarization only. On the compounds that shut down both reactions, including the clinical drugs, TMA compounds and alcohols, the potencies of shutdown and lysis exponentially increased with increasing the number of carbons in the hydrophobic region, whereas safety was affected by the structures of both hydrophilic and hydrophobic regions. These results indicate that the yeast system can easily evaluate clinical drugs, and provide a structural basis for designing compounds to shut down intracellular reactions.
Volume 28(5)
Pages 391-404
Published 2011-5-1
DOI 10.1002/yea.1846
PMID 21374719
MeSH Actins / metabolism Anesthetics, Local / chemistry Anesthetics, Local / pharmacology* Antipsychotic Agents / chemistry Antipsychotic Agents / pharmacology* Dose-Response Relationship, Drug Inhibitory Concentration 50 Phenothiazines / chemistry Phenothiazines / pharmacology* Protein Biosynthesis Saccharomyces cerevisiae / drug effects* Saccharomyces cerevisiae / metabolism Structure-Activity Relationship
IF 3.143
Times Cited 5
Pathogenic microorganisms