Chagas disease, caused by the protozoan Trypanosoma cruzi, has increased in the world due to migration, travelling and climate change; at present, the principal problem is that common trypanocidal agents have resulted in toxic or inconvenient side effects. We tested for genotoxicity in the standard (ST) and high bioactivation (HB) crosses of Drosophila wing somatic mutation and recombination test, four novel trypanocidal agents derived from 2, 4, 6-triaminquinazoline (TAQ): 2,4-diamino-6 nitro-1,3 diazonaftalene (S-1QN2-1), 2,4-diacetamino-6-amino 1,3 diazonaftalene (D-1), N⁶-(4,methoxybenzyl)quinazoline-2,4,6-triamine (GHPM) and N⁶-[4-(trifluoromethoxy)benzyl]quinazoline-2,4,6-triamine (GHPMF) at 1.9, 3.9, 7.9 and 15 µM, respectively. Also, high-pressure liquid chromatography (HPLC) analysis was run to determine the remanence of either drug in flare, and Oregon R(R)-flare flies emerged from treated larvae. S-1QN2-1 showed genotoxicity only in the ST cross, increasing the small, large and total spot frequencies at all concentrations and twin spots only at 1.9 µM; D-1 and GHPM showed significant increments of large spots only at 15 µM in the ST cross; GHPMF was not genotoxic at any concentration or either cross. In the mwh clones accumulated distribution frequencies analysis, associated with disrupted cell division, S-1QN2-1 caused alterations in the ST cross at all concentrations but only at 15 µM in the HB cross; D-1 caused alterations at 3.9, 7.9 and 15 µM in the ST cross and at 1.9 and 15 µM in the HB cross; GHPM caused alterations at 7.9 and 15 µM in the ST cross and also at 1.9, 3.9 and 7.9 µM in the HB cross; GHPMF caused those alterations at all concentrations in the ST cross and at 1.9, 3.9 and 7.9 µM in the HB cross. The HPLC results indicated no traces of either agent in the flare and Oregon R(R)-flare flies. We conclude that S-1QN2-1 is clearly genotoxic, D-1 and GHPM have an unclear genotoxicity and GHPMF was not genotoxic; all quinazoline derivatives disrupted cell division. GHPMF is a good candidate to be tested in other genotoxicity and cytotoxic bioassays. The differences in the genotoxic activity of these trypanocidal agents are correlated with differences in their chemical structure.

中文翻译：

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果蝇翼体细胞突变和重组试验中四种喹唑啉衍生的锥虫杀灭剂的遗传毒性评估。

由于迁徙，旅行和气候变化，原生动物克氏锥虫引起的恰加斯病在世界范围内有所增加；目前，主要问题是普通的锥虫杀虫剂已导致毒性或不便的副作用。我们测试了果蝇翅体细胞突变和重组测试的标准（ST）和高生物激活（HB）杂交的遗传毒性，从2、4、6-三氨基喹唑啉（TAQ）衍生出的四种新型锥虫杀灭剂：2,4-二氨基-6硝基-1,3-二氮杂萘（S-1QN2-1），2,4-二乙酰氨基-6-氨基1,3二氮杂萘（D-1），N ^6-（4，甲氧基苄基）喹唑啉-2,4,6-三胺（GHPM）和N ⁶-[4-（三氟甲氧基）苄基]喹唑啉-2,4,6-三胺（GHPMF）的浓度分别为1.9、3.9、7.9和15 µM。另外，进行高压液相色谱（HPLC）分析以确定火炬中任何一种药物的残留，并且从处理过的幼虫中产生俄勒冈火炬蝇。S-1QN2-1仅在ST杂交中显示出遗传毒性，在所有浓度下都增加了小，大和总斑点频率，仅在1.9 µM处增加了双斑点。D-1和GHPM在ST杂交中仅在15 µM处显示出大斑点的显着增加。GHPMF在任何浓度或任何交叉都不具有遗传毒性。在MWH克隆的累积分布频率分析，与细胞分裂中断有关，S-1QN2-1在所有浓度下均引起ST杂交的改变，但在HB杂交中只有15 µM的改变。D-1引起ST杂交的3.9、7.9和15 µM以及HB杂交的1.9和15 µM的变化；GHPM在ST杂交中引起了7.9和15 µM的改变，在HB杂交中引起了1.9、3.9和7.9 µM的改变；GHPMF导致ST杂交中所有浓度以及HB杂交中1.9、3.9和7.9 µM的那些改变。HPLC结果表明在火炬和俄勒冈州火炬蝇中没有任何药剂的痕迹。我们得出的结论是，S-1QN2-1具有明显的遗传毒性，D-1和GHPM具有不清楚的遗传毒性，而GHPMF没有遗传毒性。所有喹唑啉衍生物都会破坏细胞分裂。GHPMF是在其他遗传毒性和细胞毒性生物测定法中测试的良好候选者。这些锥虫杀菌剂的遗传毒性活性的差异与其化学结构的差异相关。