A new series of tetrahydroacridine derivatives with the fluorobenzoyl moiety was synthesized and evaluated for cytotoxic activity against lung cancer cell lines A549 and colorectal cancer HT29. The cytotoxic activity of the compounds was compared on the somatic cell line—EAhy926. Compounds showed high cytotoxic activity on A549 cells (IC₅₀ 183.26–68.07 μM) and HT29 cells (IC₅₀ 68.41–19.70 μM), higher than controls—etoposide (IC₅₀ 451.47 μM) toward A549 and 5-fluorouracil (IC₅₀ 1626.85 μM) against HT29. Derivative 4 was the most cytotoxic to A549, whereas for the cell lines HT29 compound 6. Selected compounds showed similar cytotoxicity to the EAhy926 cell line (IC₅₀ about 50 μM). In the hyaluronidase inhibition assay, all compounds exhibited anti-inflammatory activity, including 4 exhibiting the best inhibitory activity—IC₅₀ of 52.27 μM when the IC₅₀ heparin was 56.41 μM. Mathematical modeling was performed to determine LD₅₀ after intraperitoneal, oral, intravenous and subcutaneous administration and to predict potential mutagenicity and carcinogenicity of the compounds analyzed. Obtained results showed that tested derivatives are slightly toxic compounds, and LD₅₀ values (mg/kg) ranged from 680 to 1200 (oral rat model), the analyzed compounds have low mutagenic potential, and differences between derivatives are insignificant and very low probability of carcinogenicity. To confirm mathematical calculations, an in vivo test was carried out on a laboratory mouse model for two selected compounds. It allowed to qualify compounds: 6 to category 4 of the GHS scale, and 4 to category 3 of the GHS scale.

中文翻译：

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在体外对 A549 和 HT-29 细胞系以及在动物模型中的体内具有氟苯甲酸部分的新型四氢吖啶衍生物的生物学评估。

合成了一系列具有氟苯甲酰基部分的新四氢吖啶衍生物，并评估了其对肺癌细胞系 A549 和结肠直肠癌 HT29 的细胞毒活性。在体细胞系——EAhy926 上比较了化合物的细胞毒活性。化合物对 A549 细胞 (IC ₅₀  183.26–68.07 μM) 和 HT29 细胞 (IC ₅₀ 68.41–19.70 μM) 显示出高细胞毒活性，高于对照物 - 依托泊苷 (IC ₅₀ 451.47 μM) 对 A549 和 5-氟尿嘧啶 (IC ₅₀ 1626.85 μM ) ) 针对 HT29。衍生物4对 A549 的细胞毒性最大，而对于细胞系 HT29 化合物6。选定的化合物显示出与 EAhy926 细胞系相似的细胞毒性（IC ₅₀约 50 μM)。在透明质酸酶抑制测定中，所有化合物都表现出抗炎活性，其中4种表现出最好的抑制活性——IC ₅₀为52.27 μM，而IC ₅₀肝素为56.41 μM。进行数学建模以确定腹膜内、口服、静脉内和皮下给药后的 LD _{50并预测所分析化合物的潜在致突变性和致癌性。}所得结果表明，受试衍生物为微毒化合物，LD ₅₀值（mg/kg）从680到1200（大鼠口服模型），所分析的化合物具有低致突变潜力，衍生物之间的差异微不足道，致癌概率非常低。为了确认数学计算，在实验室小鼠模型上对两种选定的化合物进行了体内测试。它允许对化合物进行鉴定：6到 GHS 等级的第 4 类，以及4到 GHS 等级的第 3 类。