Turhan Kadir, Ozturkcan S Arda, Turgut Zuhal, Karadayi Mehmet, Gulluce Medine
Department of Chemistry, Yildiz Technical University , Istanbul , Turkey and.
Drug Chem Toxicol. 2014 Oct;37(4):365-9. doi: 10.3109/01480545.2013.866136. Epub 2013 Dec 16.
The goal of the present research was to determine the protective potential of five newly synthesized indenopyridine derivatives against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 9-aminoacridine (9-AA) induced mutagenesis. MNNG sensitive Escherichia coli WP2uvrA and 9-AA sensitive Salmonella typhimurium TA1537 were chosen as the bacterial tester strains. All of the test compounds showed significant antimutagenic activity at various tested concentrations. The inhibition rates ranged from 25.6% (Compound 2 - 1 mM/plate) to 68.2% (Compound 1 - 2.5 mM/plate) for MNNG and from 25.7% (Compound 4 - 1 mM/plate) to 76.1% (Compound 3 - 2.5 mM/plate) for 9-AA genotoxicity. Moreover, the mutagenicity of the test compounds was investigated by using the same strains. None of the test compounds has mutagenic properties on the bacterial strains at the highest concentration of 2.5 mM. Thus, the findings of the present study give valuable clues to develop new strategies for chemical prevention from MNNG and 9-AA genotoxicity by using synthetic indenopyridine derivatives.
本研究的目的是确定五种新合成的茚并吡啶衍生物对N-甲基-N'-硝基-N-亚硝基胍(MNNG)和9-氨基吖啶(9-AA)诱导的诱变的保护潜力。选择对MNNG敏感的大肠杆菌WP2uvrA和对9-AA敏感的鼠伤寒沙门氏菌TA1537作为细菌测试菌株。所有测试化合物在不同测试浓度下均表现出显著的抗诱变活性。对于MNNG,抑制率范围为25.6%(化合物2 - 1 mM/平板)至68.2%(化合物1 - 2.5 mM/平板);对于9-AA遗传毒性,抑制率范围为25.7%(化合物4 - 1 mM/平板)至76.1%(化合物3 - 2.5 mM/平板)。此外,使用相同菌株研究了测试化合物的诱变性。在最高浓度2.5 mM时,没有一种测试化合物对细菌菌株具有诱变特性。因此,本研究结果为通过使用合成茚并吡啶衍生物开发预防MNNG和9-AA遗传毒性的新化学预防策略提供了有价值的线索。