Tekiner-Gulbas B, Temiz-Arpaci O, Oksuzoglu E, Eroglu H, Yildiz I, Diril N, Aki-Sener E, Yalcin I
Faculty of Pharmacy, Pharmaceutical Chemistry Department, Ankara University, Ankara, Turkey.
SAR QSAR Environ Res. 2007 May-Jun;18(3-4):251-63. doi: 10.1080/10629360701303966.
Previously synthesized 2,5-disubstituted benzoxazole and benzimidazole derivatives, were tested for their genotoxic activity in the Bacillus subtilis rec- assay. The results revealed that 5-methyl-2-(p-aminobenzyl)benzoxazole exhibited the highest genotoxic response, which was comparable to 4-nitroquinoline 1-oxide (4-NQO), the reference agent of classical positive mutagen. Among the other tested compounds, four showed a genotoxic activity. A QSAR study revealed that structural parameters IY(C(2)H(4)) and IY(CH(2)O), indicating the bridge elements between the phenyl moiety and the fused ring system at position 2 and the quantum chemical parameter (DeltaE ), showing the difference between HOMO and LUMO energies, were found significant for enhancing the genotoxic activity in these compounds. In addition, the substituent effects on positions R and R(1) were found important for the activity as well as holding a substituent possessing a maximum length with a minimum width property on position R(1) like alkyl groups. On the other hand, substituting position R with an electron donating group instead of electron withdrawing group increased the genotoxic activity.
先前合成的2,5-二取代苯并恶唑和苯并咪唑衍生物，在枯草芽孢杆菌rec-试验中测试了它们的遗传毒性活性。结果显示，5-甲基-2-(对氨基苄基)苯并恶唑表现出最高的遗传毒性反应，这与经典阳性诱变剂4-硝基喹啉1-氧化物(4-NQO)相当。在其他测试化合物中，有四种显示出遗传毒性活性。一项定量构效关系研究表明，结构参数IY(C(2)H(4))和IY(CH(2)O)，分别表示苯部分与2位稠环系统之间的桥连元素，以及量子化学参数(ΔE)，显示最高占据分子轨道(HOMO)和最低未占分子轨道(LUMO)能量之间的差异，对于增强这些化合物的遗传毒性活性具有重要意义。此外，发现R和R(1)位上的取代基效应对于活性也很重要，并且在R(1)位上具有一个具有最大长度和最小宽度性质的取代基（如烷基）也很重要。另一方面，用供电子基团取代R位而不是吸电子基团会增加遗传毒性活性。
