Synthesis of 4‐Hydroxycoumarin‐Based Triazoles/Oxadiazoles as Novel Anticancer Agents

Abstract

Abstract A series of novel 3‐substituted‐4‐hydroxycoumarins 7 and 8 containing (5‐aryl‐1,3,4‐oxadiazol‐2‐yl)thio or (4‐amino‐5‐aryl‐4 H ‐1,2,4‐triazol‐3‐yl)thio moieties have been synthesized and evaluated as anticancer agents. The in vitro MTT assay of compounds against hepatocellular carcinoma (HepG2), breast cancer (MCF7) cells, and a human colorectal adenocarcinoma cell line with epithelial morphology (HT29) indicated that the HepG2 cells had more susceptibility to the tested compounds. Indeed, all compounds (with the exception of 7b , 7c , 7g , and 8g ) were more potent than the standard drug doxorubicin against HepG2 cells (IC 50 values=1.65–3.83 μM). Although, the better result was obtained with the oxadiazole analog 7h against HepG2 (IC 50 =1.65 μM), the N ‐amino‐triazole derivatives 8c , 8e , 8f and, 8h with IC 50 values of 1.78–6.34 μM showed potent activity against all tested cell lines. The good drug‐like properties and in vitro potency and selectivity of 4‐hydroxycoumarins 8 make them as good leads for the development of new anticancer agents.