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Journals / Türk Biyokimya Dergisi / 2015 / Cilt: 40 - Sayı: 6

Tetrahidro-naftalen-benzimidazol/tiyazolidindion retinoid türevlerinin genotoksisitesi

Genotoxicity studies of tetrahydro-naphthalenebenzimidazole/thiazolidinedione as retinoid derivatives

Erdem BÜYÜKBİNGÖL
Zeynep ATEŞ-ALAGÖZ
Mübeccel DURUSOY
Tuğba SOMAY DOĞAN
Pages
500–507
Publication Date
2022-11-05
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

For allcompounds, the induction of umuC gene expression wasfound to be almost the same for the strains that overexpressnitroreductase and O-acetyltransferase.Conclusion: None of the derivatives showed genotoxiceffects, a very important data, making them a potentialdrug candidate.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Mutagenicity is an undesirable sideeffect of clinically prescribed drugs, thus raises the questionof their potential carcinogenicity.
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Key Findings & Data:For this reason, the present study reportsthe genotoxicity of previously synthesized benzimidazole/thiazolidinedione-retinoidderivatives (Ates-Alagozand Buyukbingol, 2001; Ates-Alagoz et. al., 2009) by theumu-microplate test system.Methods: In this study, since this derivates involve nitrogroups, makes advantageous the use of the umu-test,using NM2009 and NM1011 strains especially designed fordetecting the mutagenicity of nitro compounds.
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Conclusion & Impact:For allcompounds, the induction of umuC gene expression wasfound to be almost the same for the strains that overexpressnitroreductase and O-acetyltransferase.Conclusion: None of the derivatives showed genotoxiceffects, a very important data, making them a potentialdrug candidate.
🔬Design:Research Article
📍Scope:2001 Verileri
⚙️Variables:Domain Parameters

Abstract

Objective: Mutagenicity is an undesirable sideeffect of clinically prescribed drugs, thus raises the questionof their potential carcinogenicity. Taking into accountthat nitro compounds are known for their genotoxicity,it will be considerable interest to assess the genotoxicactivities of the benzimidazole/thiazolidinedione retinoidderivatives. For this reason, the present study reportsthe genotoxicity of previously synthesized benzimidazole/thiazolidinedione-retinoidderivatives (Ates-Alagozand Buyukbingol, 2001; Ates-Alagoz et. al., 2009) by theumu-microplate test system.Methods: In this study, since this derivates involve nitrogroups, makes advantageous the use of the umu-test,using NM2009 and NM1011 strains especially designed fordetecting the mutagenicity of nitro compounds. Two bacterialstrains Salmonella typhimurium NM1011 and S. typhimuriumNM2009, expressing high levels of nitroreductase(NR) and O-acetyltransferase (O-AT) respectively, wereused in the tests. Chlorophenol red-β-D-galactopyranoside(CPRG), O-nitrophenyl- β-D-galactopyranoside (ONPG)were used as substrate in the enzyme assays along with awell-known genotoxic nitro compound, 4-nitroquinoline1-oxide (4NQO), as the positive control in the test.Results: Benzimidazole/ thiazolidinedione-retinoids thatcontain NO2group with different position on benzene ringshowed no genotoxicity in both strains with both substrates.However, using CPRG as the colorimetric substrateresulted in stronger activity than using ONPG in test conductedin both strains with all compounds. Although theβ-galactosidase activities with using CPRG were three foldhigher than ONPG, parallel results were obtained for bothsubstrates and strains with all compounds tested. For allcompounds, the induction of umuC gene expression wasfound to be almost the same for the strains that overexpressnitroreductase and O-acetyltransferase.Conclusion: None of the derivatives showed genotoxiceffects, a very important data, making them a potentialdrug candidate.

Özet

Amaç: Klinikte, mutajenite ilaçların istenmeyen yan etkilerinden birisidir, nitrolu bileşikler de genotoksik etkileriyle bilindikleri için, bu çalışmada ilaç etken maddesi olarak tasarlanmış ve daha önceden sentezlenmiş benzimidazole/tiyazolidindion retinoid türevlerinin genotoksik potansiyelleri, umu-mikroplak test sistemi ile değerlendirilmiştir.Metod: Umu-mikroplak test sistemi özel olarak nitrolu bileşiklerin mutajenitesini saptamak için tasarlanmıştır. Benzimidazol/ tiyazolidindion retinoid türevleri de nitro grubu içermektedir, bu nedenle çalışmamızda bu test sistemi seçilmiştir. Hata meyilli onarım sistemini (SoS) indükleme aktivitelerinin değerlendirildiği umu-mikroplak test sisteminde, nitrolu bileşiklere hassas olarak geliştirilmiş, NR (nitroredüktaz) enzimini normalden fazla ifade eden Salmonella typhimurium NM1011 ve O-At (o-asetiltransferaz) enzimini normalden fazla ifade eden S. typhimurium NM2009 suşları kullanılmıştır. Enzim test ortamında klorofenol-red-?-d-galaktopiranosid (CPRG) ve o-nitrofenil-?-d-galaktopiranosid (oNPG) substrat olarak ve genotoksik ajan olduğu bilinen 4-nitroquinoline 1-oxide (4NQo) de pozitif kontrol olarak kullanılmıştır.Bulgular: Benzen halkasının farklı pozisyonlarında nitro grubu içeren Benzimidazol/tiyazolidindion retinoid türevleri umu-mikroplak test sisteminde her iki suş ve her iki substratla genotoksik etki göstermemiştir. Test edilen maddelerin tümünde benzer sonuçlar elde edilmiştir. Tümü için, her iki suş ve substratla, umuC geninin ekspresyonunun indüksiyonu hemen hemen aynı bulunmuştur.Sonuç: Retinoid türevlerinin hiçbiri umu-mikroplak test sisteminde genotoksik etki göstermemiştir. Bu sonuç, ilaç adayı olarak değerlendirilmelerinde çok önemli bir veridir

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Cite This Article

BÜYÜKBİNGÖL, E., ATEŞ-ALAGÖZ, Z., DURUSOY, M., DOĞAN, T. S. (2022). Tetrahidro-naftalen-benzimidazol/tiyazolidindion retinoid türevlerinin genotoksisitesi. Türk Biyokimya Dergisi, Cilt: 40 - Sayı: 6, 500–507. https://ajindex.com/articles/621157

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