Toxicological Evaluation of Benzothiazole Derivatives Carrying Piperazine Ring

Abstract

Benzothiazole-piperazine derivatives prepared previously, 1h

and 1j are potential anticancer agents. Since the mutagenic

and genotoxic properties of anticancer drugs compose an

essential issue to be researched, this study is focused on

the analysis of the mutagenicity and genotoxicity of these

molecules. The mutagenicity of 1h and 1j were determined by

Ames test performed on Salmonella TA98 and TA100 strains.

Sample 1j was mutagenic on TA98 bacterial strain. However,

compound 1h was not mutagenic in bacterial strains TA98

and TA100 with and without S9 activation. The genotoxicity

of 1h was evaluated by the chromosomal aberration assay on

human lymphocytes. Compound 1h was also not genotoxic

in human lymphocytes in vitro. All results revealed that,

1h was not mutagenic in the two Salmonella strains tested

and was not genotoxic in chromosomal aberration assay.

Therefore, results demonstrate that the described molecule

is promising as a new anticancer drug without mutagenicity.

Also, after performing Ames test with other recommended

bacterial strains and in vivo experiments can be used safely

for the development

Keywords

• Benzothiazole,piperazine,anticancer,mutagenicity assay,genotoxicity,in vitro chromosomal aberration assay

Piperazin halkası taşıyan benzotiyazol türevlerinin toksikolojik değerlendirilmesi

Abstract

Önceki çalışmalardan elde edilen 1h ve 1j adlı bileşikler

potansiyel antikanser aktiviteye sahiptir. Antikanser

ilaçların mutajenik ve genotoksik özelliklerinin bu ilaçların

araştırılmasında temel konuyu oluşturması sebebiyle, çalışmada

söz konusu moleküllerin mutajenite ve genotoksisite analizleri

üzerinde durulmuştur. 1h ve 1j Moleküllerinin mutajeniteleri

Salmonella TA98 ve TA100 suşları ile Ames testi uygulanarak

belirlenmiştir. 1j Bileşiği TA98 bakteri suşu üzerinde mutajen

bulunmuştur. Ancak, 1h bileşiğinin TA 100 ve TA98 suşları

ile S9 varlığında ve yokluğunda mutajenik aktiviteye sahip

olmadığı gösterilmiştir. 1h Bileşiğinin genotoksisitesi insan

lenfositleri üzerinde yapılan kromozomal aberasyon testi

ile değerlendirilmiş olup genotoksik bir risk oluşturmadığı

saptanmıştır. Bütün sonuçlar değerlendirildiğinde, 1h’nin iki

farklı Salmonella suşu üzerinde yapılan çalışmada mutajenik

aktivitesi olmadığı ve kromozom aberasyon testinde genotoksik

olmadığı saptanmıştır. Bu nedenle, sonuçları belirtilen

molekülün mutajenik ve genotoksik etkileri olmadığı için yeni

bir antikanser ilaç olarak umut verici olduğu görülmüştür.

Güvenle kullanılabilecek antikanser aktivite sergileyen yeni bir

molekülün varlığını göstermek için yukarıdaki analizlere ek

olarak Ames testi tavsiye edilen diğer bakteri suşlarıyla ve in

vivo deneylerle desteklenmelidir.

Keywords

• Benzotiyazol,piperazin,antikanser,mutajenite deneyi,genotoksisite

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