In the current report, we have rationally designed a series of uracil-coumarin based bifunctional molecular hybrids roped by 1,2,3-triazole moiety. The designed compounds were synthesized and tested against a panel of six human cancer cell lines namely Colo-205, MCF-7, A-549, PA-1, PC-3 and Hela cells by Sulforhodamine B assay. The results indicated that the hybrid molecules can specifically inhibit the MCF-7 cancer cell proliferation amongst which A-2 was found to be most potent hybrid (GI₅₀ = 1.55 µM) with fluorine atom as R with two carbon chain length between triazole and coumarin moieties. Cell cycle analysis revealed that A-2 significantly arrest the G2/M phase to inhibit proliferation of MCF-7 cells. Due to its mitotic arrest, A-2 was further analyzed to predict its various binding interactions within the active site of tubulin, which revealed its best binding pattern within the vinblastine binding site. In addition to this, antibacterial potential of all the synthetics was also evaluated which resulted in two hit lead molecules A-2 (MIC = 11.7 μg/mL) and A-3 (MIC = 7.23 μg/mL) that can significantly inhibit the bacterial strain Staphylococcus aureus comparable to that of standard drug levofloxacin (MIC = 3.12 μg/mL). Binding interactions within the active site of dihydrofolate reductase (DHFR) were also streamlined by using molecular docking studies. Overall studies revealed some interesting features of synthetics to be active which stated that, the compounds with electronegative atom on R and compounds with two carbon chain length between triazole and coumarin showed best results.

在本报告中，我们合理地设计了一系列以1,2,3-三唑部分为基础的基于尿嘧啶-香豆素的双功能分子杂种。合成了设计的化合物，并通过磺基罗丹明B试验针对六种人类癌细胞系（即Colo-205，MCF-7，A-549，PA-1，PC-3和Hela细胞）进行了测试。结果表明，杂合分子可以特异性抑制MCF-7癌细胞的增殖，其中A-2是最有效的杂合体（GI ₅₀  = 1.55 µM），氟原子为R，三唑和香豆素之间的碳链长度为两个部分。细胞周期分析表明，A-2可以明显阻滞G2 / M期，从而抑制MCF-7细胞的增殖。由于有丝分裂被捕，A-2进一步分析以预测其在微管蛋白活性位点内的各种结合相互作用，这揭示了其在长春碱结合位点内的最佳结合模式。除此之外，还评估了所有合成物的抗菌潜力，结果发现两个命中的铅分子A-2（MIC = 11.7μg/ mL）和A-3（MIC = 7.23μg/ mL）可以显着抑制细菌。菌株金黄色葡萄球菌相当于标准药物左氧氟沙星（MIC = 3.12μg/ mL）。通过使用分子对接研究，还简化了二氢叶酸还原酶（DHFR）活性位点内的结合相互作用。整体研究表明，合成物具有一些有趣的活性特征，这些特征表明，R上带有负电性原子的化合物以及三唑和香豆素之间具有两个碳链长度的化合物表现出最好的效果。