在本研究中，合成了一系列新的喹唑啉-2,4,6-三胺衍生物，以探索它们作为黄嘌呤氧化酶(XO)抑制剂、超氧自由基清除剂以及对其毒理学特性的筛选。在所有合成的化合物中，B1对牛黄嘌呤氧化酶(bXO)表现出比丙戊酸醛酸(Uloric)更好的抑制活性(IC50分别为1.56μM和6.99μM)。作为超氧自由基清除剂，B1、B2和B13的效果优于丙戊酸醛酸(分别为97.3%、82.1%、87.4%和69.4%)。关于毒理学特性，B1在HCT-15癌细胞上的细胞毒性较甲氨蝶呤(methotrexate)低。雌性和雄性小鼠细胞中获得的凋亡结果显示，B1和B2的平均诱导凋亡频率与二氧化铬(CrO3)（阳性对照）相似；而B13的凋亡诱导效果与二甲基亚砜(DMSO)和对照组相似。最后，与二氧化铬相比，B1、B2和B13在小鼠微核模型中没有诱发基因毒性作用。© 2023 The Authors. ChemMedChem由Wiley-VCH GmbH出版。

In this work, a new set of quinazolin-2,4,6-triamine derivatives were synthesized to explore their potential biological activity as xanthine oxidase (XO) inhibitors, superoxide scavengers and screening of their toxicological profile. Among all the synthesized compounds, B1 exhibited better inhibitory activity against bovine xanthine oxidase (bXO) than allopurinol (IC50 =1.56 μM and IC50 =6.99 μM, respectively). As superoxide scavengers, B1, B2 and B13 exhibited a better effect than allopurinol (97.3 %, 82.1 %, 87.4 % and 69.4 %, respectively). Regarding the toxicological profile, B1 was less cytotoxic than methotrexate on HCT-15 cancer cells. Apoptosis results obtained in cells of female and male mice, showed that B1 and B2 presented a similar behaviour to CrO3 (positive control) with respect to the average frequency to induce apoptosis; while B13 apoptosis induced effect was similar to DMSO and control group. Finally, B1, B2, B13 did not induce genotoxicity in a micronuclei murine model compared to CrO3 .© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.