Comparative evaluation of mutagenic, genotoxic, cytotoxic, and antimicrobial effects of flavour and fragrance aldehydes, ketones, oximes, and oxime ethers

Lucyna Balcerzak; Alicja K Surowiak; Katarzyna Groborz; Sylwia Stróżak; Katarzyna Piekarska; Daniel J Strub

doi:10.1016/j.tox.2023.153510

Comparative evaluation of mutagenic, genotoxic, cytotoxic, and antimicrobial effects of flavour and fragrance aldehydes, ketones, oximes, and oxime ethers

Toxicology. 2023 May 15:490:153510. doi: 10.1016/j.tox.2023.153510. Epub 2023 Apr 13.

Authors

Lucyna Balcerzak¹, Alicja K Surowiak¹, Katarzyna Groborz², Sylwia Stróżak³, Katarzyna Piekarska³, Daniel J Strub⁴

Affiliations

¹ Department of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wroclaw, Poland.
² Department of Physiological Chemistry, Genentech, South San Francisco, CA, USA.
³ Department of Environmental Protection Engineering, Faculty of Environmental Engineering, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, Wrocław, 50-370, Poland.
⁴ Department of Chemical Biology and Bioimaging, Wroclaw University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370 Wroclaw, Poland. Electronic address: daniel.strub@pwr.edu.pl.

PMID: 37059348
DOI: 10.1016/j.tox.2023.153510

Abstract

Despite the large number of odoriferous compounds available, new ones with interesting olfactory characteristics are desired due to their potentially high commercial value. Here, we report for the first time mutagenic, genotoxic, and cytotoxic effects, and antimicrobial properties of low-molecular fragrant oxime ethers, and we compare their properties with corresponding oximes and carbonyl compounds. 24 aldehydes, ketones, oximes, and oxime ethers were evaluated for mutagenic and cytotoxic effects in Ames (using Salmonella typhimurium strains TA 98 with genotype hisD3052, rfa, uvrB, pKM101, and TA100 with genotype hisG46, rfa, uvrB, pKM101, concentration range: 0.0781-40 mg/mL) and MTS (using HEK293T cell line concentration of tested substances: 0.025 mM) assays. Antimicrobial evaluation was carried out against Bacillus cereus (ATCC 10876), Staphylococcus aureus (ATCC 6538), Enterococcus hirae (ATCC 10541), Pseudomonas aeruginosa (ATCC 15442), Escherichia coli (ATCC 10536), Legionella pneumophila (ATCC 33152); Candida albicans (ATCC 10231) and Aspergillus brasiliensis (ATCC 16404) with concentration range of tested substances 9.375 - 2.400 mg/mL. Furthermore, 5 representatives of carbonyl compounds, oximes, and an oxime ether (stemone, buccoxime, citral, citral oxime, and propiophenone oxime O-ethyl ether) were evaluated for genotoxic properties in SOS-Chromotest (concentration range: 7.8·10^-5 - 5·10^-3 mg/mL). All of the tested compounds did not exhibit mutagenic, genotoxic, or cytotoxic effects. Oximes and oxime ethers showed relevant antimicrobial activity against pathogenic species (P. aeruginosa, S. aureus, E.coli, L. pneumophila, A. brasiliensis, C. albicans) in the MIC range 0.075 - 2.400 mg/mL compared to the common preservative methylparaben with the MIC range 0.400-3.600 mg/mL. Our study shows that oxime ethers have the potential to be used as fragrant agents in functional products.

Keywords: Antimicrobial activity; Cytotoxicity; Fragrance; Genotoxicity; Oxime; Oxime ether.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehydes / toxicity
Anti-Infective Agents* / toxicity
Antifungal Agents*
DNA Damage
Ethers / toxicity
HEK293 Cells
Humans
Ketones / pharmacology
Microbial Sensitivity Tests
Mutagens
Odorants
Oximes / toxicity
Staphylococcus aureus

Substances

citral
Antifungal Agents
Ethers
Mutagens
Oximes
Ketones
Aldehydes
Anti-Infective Agents