Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes

• Published in: Pharmaceutical biology Vol. 55; no. 1; pp. 1228 - 1233
• Main Authors: Avuloğlu-Yılmaz, Ece, Yüzbaşıoğlu, Deniz, Özçelik, Azime Berna, Ersan, Seyhan, Ünal, Fatma
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2017; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Adult; Antifibrinolytic agents; Cells, Cultured; Chromosome aberrations; DNA damage; DNA Damage - drug effects; DNA Damage - genetics; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical - methods; Female; Genotoxicity; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; lymhocyte culture; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - physiology; Male; Mutagenicity Tests - methods; Sodium hydroxide; Thiazines - toxicity; Thiones - toxicity; Tranexamic acid; genotoxicity; Tranexamic acid; lymhocyte culture; DNA damage
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2017.1296000

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 H 2 O 2 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.