Abstract

The influence of the UV–Vis radiation on the toxicity of agomelatine, loxapine, clozapine and tiapride was studied. The phototransformation procedure was conducted with the use of simulated solar radiation. In the case of each compound irradiation time necessary to decompose half of the initial concentration was chosen. The embryotoxicity and acute toxicity were evaluated using zebrafish (Danio rerio) embryos and larvae. The mutagenicity assay was done with the use of a micro-plate Ames test. Generally, the embryotoxicity decreased after the irradiation procedure. The obtained results showed that tiapride is the least toxic compound to zebrafish, however, its toxicity toward larvae increases after the irradiation. Similarly, the mutagenic potential of the mixture of tiapride photoproducts is higher than in the case of parent compound. The phototransformation of loxapine resulted in the change of the acute toxicity profile and increased the rate of reverse mutations in the Ames test. Oppositely, the irradiation of agomelatine caused the decrease of mutagenic potential and acute toxicity was also lower in the postirradiated mixture. The phototransformation of clozapine did not alter the mutagenicity and decreased the acute toxicity to the zebrafish larvae. In silico calculations showed a satisfactory prediction ability in some instances, especially in the case of mutagenic potential of the tiapride phototransformation products.

摘要

研究了UV-Vis辐射对阿戈美拉汀，洛沙平，氯氮平和噻虫普利的毒性的影响。使用模拟的太阳辐射进行光转化程序。在每种化合物的情况下，选择分解初始浓度一半所需的照射时间。使用斑马鱼（Danio rerio）评估了胚胎毒性和急性毒性。）胚胎和幼虫。致突变性测定是使用微板Ames试验进行的。通常，照射后胚胎毒性降低。获得的结果表明，噻虫嗪是对斑马鱼毒性最小的化合物，但是，辐照后其对幼虫的毒性增加。相似地，替帕必利光产物混合物的诱变潜能高于母体化合物的诱变潜能。在Ames试验中，洛沙平的光转化导致急性毒性特征的改变，并增加了反向突变的发生率。相反，阿戈美拉汀的辐照引起诱变潜能的降低，并且在辐照后的混合物中急性毒性也较低。在计算机上，计算机计算显示出令人满意的预测能力，在某些情况下，尤其是在替阿必利光转化产物具有诱变潜力的情况下。