Powroźnik Beata, Słoczyńska Karolina, Canale Vittorio, Grychowska Katarzyna, Zajdel Paweł, Pękala Elżbieta
Department of Pharmaceutical Biochemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, Poland.
J Appl Genet. 2016 May;57(2):263-70. doi: 10.1007/s13353-015-0322-5. Epub 2015 Oct 6.
Determination of the mutagenic and genotoxic liability of biologically active compounds is of great concern for preliminary toxicity testing and drug development. In this study, we focused on the evaluation of the mutagenic and genotoxic effects of selected arylsulfonamide derivatives of aryloxyethyl piperidines and pyrrolidines (1-8), classified as 5-HT7 receptor antagonist with antidepressant and procognitive properties, using in silico and in vitro methods: the Vibrio harveyi assay and the SOS/umu-test (umuC Easy CS test). Finally, the antimutagenic potential of tested compounds was evaluated with the V. harveyi assay. It was demonstrated that none of the examined compounds produced a positive response in in vitro assays and these results were in line with in silico prediction. Additionally, all the tested compounds demonstrated various antimutagenic potential, with compound 1 (5-chloro-N-((1-(2-phenoxyethyl)piperidin-4-yl)methyl)thiophene-2-sulfonamide) being the most active against NQNO-induced mutagenicity.
生物活性化合物的诱变性和遗传毒性评估对于初步毒性测试和药物开发至关重要。在本研究中,我们重点评估了选定的芳氧基乙基哌啶和吡咯烷的芳基磺酰胺衍生物(1-8)的诱变性和遗传毒性作用,这些衍生物被归类为具有抗抑郁和促认知特性的5-HT7受体拮抗剂,采用了计算机模拟和体外方法:哈维氏弧菌试验和SOS/umu试验(umuC简易CS试验)。最后,用哈维氏弧菌试验评估了受试化合物的抗诱变潜力。结果表明,所检测的化合物在体外试验中均未产生阳性反应,这些结果与计算机模拟预测一致。此外,所有受试化合物均表现出不同的抗诱变潜力,其中化合物1(5-氯-N-((1-(2-苯氧基乙基)哌啶-4-基)甲基)噻吩-2-磺酰胺)对NQNO诱导的诱变活性最强。