Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes
Context: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared w...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2017-01-01
|
Series: | Pharmaceutical Biology |
Subjects: | |
Online Access: | http://dx.doi.org/10.1080/13880209.2017.1296000 |
id |
doaj-6240af07704d45bc800639790c1ef803 |
---|---|
record_format |
Article |
spelling |
doaj-6240af07704d45bc800639790c1ef8032020-11-25T03:48:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162017-01-015511228123310.1080/13880209.2017.12960001296000Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytesEce Avuloğlu-Yılmaz0Deniz Yüzbaşıoğlu1Azime Berna Özçelik2Seyhan Ersan3Fatma Ünal4Gazi UniversityGazi UniversityGazi UniversityGazi UniversityGazi UniversityContext: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug. Objectives: In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Materials and methods: Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00 μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48 h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H2O2 for isolated lymphocytes) were also maintained. Results: While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48 h, 25 μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25 μg/mL, 48 h). It significantly decreased the MI in all the concentrations at 24 h (except 0.78 μg/mL) and in the highest three concentrations at 48 h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index. Discussion and conclusion: Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes.http://dx.doi.org/10.1080/13880209.2017.1296000tranexamic acidgenotoxicitydna damagelymhocyte culture |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ece Avuloğlu-Yılmaz Deniz Yüzbaşıoğlu Azime Berna Özçelik Seyhan Ersan Fatma Ünal |
spellingShingle |
Ece Avuloğlu-Yılmaz Deniz Yüzbaşıoğlu Azime Berna Özçelik Seyhan Ersan Fatma Ünal Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes Pharmaceutical Biology tranexamic acid genotoxicity dna damage lymhocyte culture |
author_facet |
Ece Avuloğlu-Yılmaz Deniz Yüzbaşıoğlu Azime Berna Özçelik Seyhan Ersan Fatma Ünal |
author_sort |
Ece Avuloğlu-Yılmaz |
title |
Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes |
title_short |
Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes |
title_full |
Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes |
title_fullStr |
Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes |
title_full_unstemmed |
Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes |
title_sort |
evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2h-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes |
publisher |
Taylor & Francis Group |
series |
Pharmaceutical Biology |
issn |
1388-0209 1744-5116 |
publishDate |
2017-01-01 |
description |
Context: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug. Objectives: In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Materials and methods: Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00 μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48 h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H2O2 for isolated lymphocytes) were also maintained. Results: While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48 h, 25 μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25 μg/mL, 48 h). It significantly decreased the MI in all the concentrations at 24 h (except 0.78 μg/mL) and in the highest three concentrations at 48 h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index. Discussion and conclusion: Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes. |
topic |
tranexamic acid genotoxicity dna damage lymhocyte culture |
url |
http://dx.doi.org/10.1080/13880209.2017.1296000 |
work_keys_str_mv |
AT eceavulogluyılmaz evaluationofgenotoxiceffectsof3methyl54carboxycyclohexylmethyltetrahydro2h135thiadiazine2thioneonhumanperipherallymphocytes AT denizyuzbasıoglu evaluationofgenotoxiceffectsof3methyl54carboxycyclohexylmethyltetrahydro2h135thiadiazine2thioneonhumanperipherallymphocytes AT azimebernaozcelik evaluationofgenotoxiceffectsof3methyl54carboxycyclohexylmethyltetrahydro2h135thiadiazine2thioneonhumanperipherallymphocytes AT seyhanersan evaluationofgenotoxiceffectsof3methyl54carboxycyclohexylmethyltetrahydro2h135thiadiazine2thioneonhumanperipherallymphocytes AT fatmaunal evaluationofgenotoxiceffectsof3methyl54carboxycyclohexylmethyltetrahydro2h135thiadiazine2thioneonhumanperipherallymphocytes |
_version_ |
1724499091190185984 |