Structural analysis of compounds with actions similar to local anesthetics and antipsychotic phenothiazines in 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. Copyright © 2011 John Wiley & Sons, Ltd.
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The antipsychotic phenothiazine and the antidepressant nortriptyline have been reported to disrupt cell membranes.
“The antipsychotic phenothiazine and the antidepressant nortriptyline have also been reported to disrupt cell membranes [72,104,105].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [105]
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Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54 · see citing works
Caldara, M., & Marmiroli, N. (2020) · Microorganisms · doi:10.3390/microorganisms8050742 · Cited by 8 · see citing works
- Authors
- Uesono, Y., Toh‐e, A., Kikuchi, Y., & Terashima, I.
- Affiliations
- The University of Tokyo (JP)
- Chiba University (JP)
- Gakushuin University (JP)
- Corresponding author
- Uesono, Yukifumi
- Venue
- Yeast
- Publisher
- Wiley
- Published
- 2011-03-04
- Volume
- 28
- Issue
- 5
- Pages
- 391-404
- ISSN
- 0749-503X (ISSN-L)
- 1097-0061
- OpenAlex
- W2041087737
- Cited by
- 12
- References
- 37
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2014: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Yeast (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21570003)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- local anesthetics, phenothiazines, actin polarization, translation initiation, yeast cell lysis, amphiphilic molecules, structure-activity relationship, alkyl chain length, surfactant activity, drug safety
- MeSH terms
- Actins, Anesthetics, Local, Dose-Response Relationship, Drug, Phenothiazines, Saccharomyces cerevisiae, Structure-Activity Relationship, Antipsychotic Agents, Protein Biosynthesis, Inhibitory Concentration 50
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