Abstract
[1-(2-isopropyl-5-methylphenoxy)-3-(yridine-3-ylmethylamino)propan-2-ol] is a novel oxipropanolamine derivative. It had been synthesized in a previous study with the idea that could be a prodrug and determined to show anti-α-glycosidase, antiacetylcholinesterase, anticarbonic anhydrase and antibacterial activities. However, to suggest it as a drug candidate, genotoxicity data related to it should be available. Thus, in this research, we aimed to evaluate its genotoxicity. We performed the chromosomal aberration and micronucleus tests in human peripheral lymphocytes. In all tests, lymphocyte cultures were treated with four concentrations (50, 25, 12.5, 6.25 μg/mL) of this derivative. According to our results, it significantly increased the chromosomal abnormalities at 25 and 50 μg/mL concentrations both 24 h and 48 h periods. Also, it significantly decreased the mitotic index at all concentrations. On the other hand, it significantly increased the micronucleus frequencies at 6.25, 12.5, and 25 μg/mL concentrations. In micronucleus test, no binucleate cells were detected at the highest concentration (50 μg/mL) and a total number of 4000 binucleate cells couldn’t be reached at the second-highest concentration (25 μg/mL). These results evaluated together, we can suggest that the test substance is cytotoxic and aneugenic at all used concentrations in human peripheral lymphocytes. Also, it’s clastogenic and genotoxic at high application concentrations.
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Abbreviations
- anti-AChE:
-
Anti-acetylcholinesterase
- anti-CA:
-
Anti-carbonic anhydrase
- BN:
-
Binucleated
- CA:
-
Chromosomal aberrations
- csb:
-
Chromosome breaks
- ctb:
-
Chromatid break
- cte:
-
Chromatid exchanges
- dc:
-
Dicentric chromosomes
- DMSO:
-
Dimethyl sulfoxide
- er:
-
Endoredublication
- f:
-
Fragment
- LC50:
-
50% lethal concentration
- μg/mL:
-
Microgram/ml
- MI:
-
Mitotic index
- MN:
-
Micronucleus
- NC:
-
Negative control
- PC:
-
Positive control
- SC:
-
Solvent control
- SCE:
-
Sister chromatid exchange
- scu:
-
Sister chromatid union
- SE:
-
Standard error
- TS:
-
Test substance
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Acknowledgments
This research was approved by the Non-Invasive Research Ethics Committee of Sakarya University, Faculty of Medicine (03/01/2019-E.87). In addition, this study is performed according to the Declaration of Helsinki and an informed written consent form was obtained from donors who donated blood.
Funding
This study was supported by Sakarya University Scientific Research Projects Commission Presidency, Sakarya, Turkey (Project No: 2019-7-24-40).
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Meredova, G., Yıldız, E., Şen, S. et al. Genotoxicity of a novel thymol bearing oxipropanolamine derivative in human peripheral lymphocytes. Biologia 77, 559–567 (2022). https://doi.org/10.1007/s11756-021-00965-w
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DOI: https://doi.org/10.1007/s11756-021-00965-w