Abuelizz Hatem A, Awad Hanem M, Marzouk Mohamed, Nasr Fahd A, Alqahtani Ali S, Bakheit Ahmed H, Naglah Ahmed M, Al-Salahi Rashad
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University PO Box 2457 Riyadh 11451 Saudi Arabia
Department of Tanning Materials and Leather Technology, National Research Centre 33 El-Bohouth St. (Former El-Tahrir St.), Dokki Cairo 12622 Egypt.
RSC Adv. 2019 Jun 17;9(33):19065-19074. doi: 10.1039/c9ra03151k. eCollection 2019 Jun 14.
A series of 4-(1-1,2,4-triazol-1-yl)benzoic acid hybrids (1-17) was successfully synthesized and their structures were established by NMR and MS analysis. cytotoxic evaluation indicated that some of the hybrids exhibited potent inhibitory activities against MCF-7 and HCT-116 cancer cell lines, with IC values ranging from 15.6 to 23.9 µM, compared with reference drug doxorubicin (19.7 and 22.6 µM, respectively). Notably, the most potent compounds, 2, 5, 14, and 15, not only exhibited an obvious improvement in IC values, but demonstrated very weak cytotoxic effects toward normal cells (RPE-1) compared with doxorubicin. A further investigation showed that compounds 2 and 14 clearly inhibited the proliferation of MCF-7 cancer cells by inducing apoptosis. In addition, these hybrids showed acceptable correlation with bioassay results in regression plots generated by 2D QSAR models. Our results indicated that 1,2,4-triazole benzoic acid hybrids could be used as a structural optimization platform for the design and development of more selective and potent anticancer molecules.
成功合成了一系列4-(1-1,2,4-三唑-1-基)苯甲酸衍生物(1-17)，并通过核磁共振和质谱分析确定了它们的结构。细胞毒性评估表明，与参比药物阿霉素(分别为19.7和22.6 μM)相比，其中一些衍生物对MCF-7和HCT-116癌细胞系表现出有效的抑制活性，IC值范围为15.6至23.9 μM。值得注意的是，最有效的化合物2, 5, 14和15不仅IC值有明显改善，而且与阿霉素相比，对正常细胞(RPE-1)的细胞毒性作用非常弱。进一步研究表明，化合物2和14通过诱导凋亡明显抑制MCF-7癌细胞的增殖。此外，在二维定量构效关系模型生成的回归图中，这些衍生物与生物测定结果显示出良好的相关性。我们的结果表明，1,2,4-三唑苯甲酸衍生物可作为一个结构优化平台，用于设计和开发更具选择性和强效的抗癌分子。
