Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, Egypt.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):1346-1363. doi: 10.1080/14756366.2022.2072308.
A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones were synthesised as potential anticancer agents. Hybrids exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds displayed ICs ranged from 2.53-8.67 µM, 8.67-62.47 µM, and 4.19-24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC values of 1.22, 0.88, and 4.15 µM. Compounds and were the most potent against HCT116 with IC values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC = 1.22 µM). Also, hybrids and exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.
一系列新型 1,2,3-三唑连接的环丙沙星查耳酮被合成作为潜在的抗癌剂。杂种表现出对结肠癌细胞显著的增殖抑制活性。化合物对 HCT116、HT29 和 Caco-2 细胞的 IC 范围分别为 2.53-8.67 μM、8.67-62.47 μM 和 4.19-24.37 μM，而阿霉素的 IC 值分别为 1.22、0.88 和 4.15 μM。化合物和对 HCT116 的活性最强，IC 值分别为 3.57、4.81、4.32、4.87 和 2.53 μM，与阿霉素（IC = 1.22 μM）相比。此外，杂种和对拓扑异构酶 I、II 和微管蛋白聚合具有显著的抑制活性。它们增加了 γH2AX 的蛋白表达水平，表明 DNA 损伤，并使 HCT116 停滞在 G2/M 期，可能通过 ATR/CHK1/Cdc25C 途径。因此，新型环丙沙星杂种可作为进一步研究的潜在先导化合物，作为新型抗癌药物来对抗结直肠癌。
