Synthesis and Antiproliferative Evaluation of New 1,3,5‐Trisubstituted 1,2,4‐Triazole Derivatives against Glioblastoma Cell Lines

Abstract

AbstractA series of novel 1,3,5‐trisubstituted‐1,2,4‐triazole derivatives were successfully synthesized from the starting materials of caffeic acid (CA) and ferulic acid (FA) in moderate to good yields (45–71 %). All novel compounds were screened for antiproliferative activity against three glioblastoma (GB) cell lines. Several compounds exhibited improved cytotoxic activities compared to the caffeic acid phenethyl ester (CAPE). Among the novel derivatives, 4‐(2‐(1‐benzyl‐3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)vinyl)‐2‐methoxyphenol (4) exhibited the most potent activity against the U87G, T98G and LN229 cell lines. Western blot results showed significantly reduced poly(ADP‐ribose) polymerase (PARP) and increased the Bcl‐2‐associated X (Bax) protein levels in T98G cells. Also, flow cytometry results using Annexin‐V/Propidium Iodide (PI) staining indicated that apoptosis was induced in T98G cells. It was found to be a promising drug candidate with strong physicochemical and bioavailability properties as a result of SwissADME calculations. These results show that novel compounds containing a 1,2,4‐triazole moiety have a good antiproliferative activity on GB cells.