Pedrood Keyvan, Taayoshi Fahimeh, Moazzam Ali, Iraji Aida, Yavari Ali, Ansari Samira, Sajjadi-Jazi Sayed Mahmoud, Mohajeri-Tehrani Mohammad Reza, Garmsiri Nadia, Haghpanah Vahid, Soleymanibadi Meysam, Larijani Bagher, Hamedifar Haleh, Adibpour Neda, Mahdavi Mohammad
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Heliyon. 2023 Feb 4;9(2):e13528. doi: 10.1016/j.heliyon.2023.e13528. eCollection 2023 Feb.
A novel series of quinazoline-based agents bearing triazole-acetamides were designed and synthesized. All the obtained compounds were tested for cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was (X = 4-OCH and R = H) with IC values of 10.72 and 5.33 μM after 48 and 72 h compared with doxorubicin with IC values of 1.66 and 1.21 μM, respectively. The same trend was seen in the HepG2 cancerous cell line in which recorded the best results with IC values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that with IC = 21.29 μM (48 h) exhibited the best activity, while compounds (IC = 11.32 μM) and (IC = 12.96 μM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC values of 1.15 and 0.82 μM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.
设计并合成了一系列新型的含三唑乙酰胺的喹唑啉类药物。对所有得到的化合物进行了细胞毒性活性测试，检测其在48小时和72小时后对三种人类癌细胞系HCT - 116、MCF - 7和HepG2以及一种正常细胞系WRL - 68的作用。结果表明，喹唑啉 - 氧甲基三唑化合物表现出中等至良好的抗癌潜力。对HCT - 116最具活性的衍生物是（X = 4 - OCH且R = H），48小时和72小时后的IC值分别为10.72和5.33 μM，相比之下阿霉素的IC值分别为1.66和1.21 μM。在HepG2癌细胞系中也观察到了相同的趋势，其中该衍生物在48小时和72小时后的IC值分别为17.48和7.94，表现出最佳结果。对MCF - 7的细胞毒性分析表明，IC = 21.29 μM（48小时）的化合物表现出最佳活性，而化合物（IC = 11.32 μM）和（IC = 12.96 μM）在72小时后是最有效的细胞毒性药物。作为阳性对照的阿霉素在48小时和72小时后的IC值分别为1.15和0.82 μM。值得注意的是，所有衍生物对正常细胞系的毒性都有限。此外，还进行了对接研究以了解这些新型衍生物与可能靶点之间的相互作用。
