Abstract A new series of 1,4-disubstituted-1,2,3-triazolethymine derivatives ( VIa – e ) were synthesized and characterized by spectroscopic studies. The in vitro cytotoxic activities of selected compounds against human cancer cell line (MDA-MB 231) were evaluated by MTT assay. 4-Azido- N- substituted-benzenesulfonamides ( Vc – e ) and 4,4'-(4,4'-((5-methyl-2,4-dioxopyrimidine-1,3(2 H ,4 H )-diyl)bis(methylene))-bis(1 H -1,2,3-triazole-4,1-diyl))-bis( N -(4-methyl pyrimidin-2-yl)benzenesulfonamide) ( VIc ) displayed a significant cytotoxic activity with IC 50 values of 1.61, 1.41, 1.61 and 1.81 μM, respectively. Molecular docking study of 4‑azido- N -(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide ( Vd ) and 4,4'-(4,4'-((5-methyl-2,4-dioxopyrimidine-1,3(2 H ,4 H )-diyl)bis(methylene))-bis(1 H -1,2,3-triazole-4,1-diyl))-bis ( N -(4-methyl pyrimidin-2-yl)benzenesulfonamide) ( VIc ) showed hydrogen bonding with the amino acid residues of the receptors 1X7R and 1A53, respectively. These derivatives are useful as starting points for further study of new anticancer drugs and to confirm the potential of triazole-sulfonamide analogues as lead compounds in anticancer drug discovery. In addition, 1,4-disubstituted-1,2,3-triazolethymine derivatives ( VIa – e ) were evaluated in vitro for antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. The results showed that 1,4-disubstituted-1,2,3-triazolethymine derivatives ( VIc – e ) possess a potent activity against HIV-1 replication with IC 50 values of 11.42, ≥15.25,and 14.36 μM, SI > 4, ≤6, >9, respectively.

中文翻译：

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新型 1,4-二取代-1,2,3-三唑胸腺嘧啶衍生物的点击合成、分子对接、对乳腺癌的细胞毒性 (MDA-MB 231) 和抗 HIV 活性

摘要 合成了一系列新的 1,4-二取代-1,2,3-三唑胸腺嘧啶衍生物 (VIa – e)，并通过光谱研究对其进行了表征。通过 MTT 测定评估所选化合物对人癌细胞系 (MDA-MB 231) 的体外细胞毒活性。4-叠氮基-N-取代的苯磺酰胺 (Vc – e ) 和 4,4'-(4,4'-((5-methyl-2,4-dioxopyrimidine-1,3(2 H ,4 H )-diyl )双(亚甲基))-双(1H-1,2,3-三唑-4,1-二基))-双(N-(4-甲基嘧啶-2-基)苯磺酰胺)(VIc)显示出显着的细胞毒活性，IC 50 值分别为 1.61、1.41、1.61 和 1.81 μM。4-叠氮基-N-(4,6-二甲基嘧啶-2-基)苯磺酰胺(Vd)和4,4'-(4,4'-((5-methyl-2,4-dioxopyrimidine-1))的分子对接研究,3(2 H ,4 H )-二基)双(亚甲基))-双(1 H -1,2,3-三唑-4, 1-二基))-双(N-(4-甲基嘧啶-2-基)苯磺酰胺)(VIc)分别与受体1X7R和1A53的氨基酸残基形成氢键。这些衍生物可用作进一步研究新抗癌药物的起点，并证实三唑磺胺类似物作为抗癌药物发现中的先导化合物的潜力。此外，在体外评估了 1,4-二取代-1,2,3-三唑胸腺嘧啶衍生物 (VIa – e) 对 MT-4 细胞中 HIV-1 和 HIV-2 复制的抗病毒活性。结果表明，1,4-二取代-1,2,3-三唑胸腺嘧啶衍生物 (VIc – e) 具有有效的抗 HIV-1 复制活性，IC 50 值为 11.42、≥15.25 和 14.36 μM，SI > 4，分别≤6、>9。