Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

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.