Novel 3(2H)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity in vivo and anti-proliferative effects against HCT116 cell lines in vitro. Artemia salina lethality test provided LC50 values >100 µg/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model in vivo of cancer cell microenvironment. Moreover, the kinurenic acid level after treatment with these newly synthesised compounds was monitored as a marker of anti-proliferation in colon carcinoma models. The IC50 values obtained for the best-in-class compounds were comparable to that of daunorubicin as a reference drug. Conversely, these compounds were not able to counteract the spontaneous migration of human cancer HCT116 cell line in the wound healing paradigm.

中文翻译：

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新型 3(2H)-哒嗪酮衍生物作为无毒抗人结肠癌 HCT116 细胞增殖化合物的合成和生物学评价。

设计、合成了新型3(2H)-哒嗪酮衍生物，并以令人满意的产率进行了评估，并在不同的实验测定中进行了评估，以评估其初步的体内毒性和体外对HCT116细胞系的抗增殖作用。卤虫致死率测试得出所有化合物的 LC50 值 >100 µg/mL。连续的测定表明，一些化合物被赋予了对 HCT116 细胞有希望的抗增殖作用，单独使用或通过血清素作为促炎因子刺激，以模拟体内癌细胞微环境的炎症模型。此外，监测用这些新合成的化合物治疗后的激尿酸水平，作为结肠癌模型中抗增殖的标志物。同类最佳化合物获得的 IC50 值与作为参考药物的柔红霉素相当。相反，这些化合物不能抵消伤口愈合范例中人类癌症 HCT116 细胞系的自发迁移。