A series of new 1,3,4-oxadiazole derivatives were synthesized and evaluated for their antioxidant, cytotoxic, and apoptosis activities. Antioxidant activity was determined in vitro using free radical scavenging (2,2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power assays. Most of the synthesized compounds exhibited significant antioxidant activities. Compound 3 showed the most potent antioxidant activity, comparable to the antioxidants used as positive controls—quercetin, BHT, trolox, rutin, and ascorbic acid. Compound 1 displayed high radical scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl assay, with an half-maximum inhibitory concentration (IC50) = 2.22 ± 0.01 µg/mL. Cytotoxic activities were evaluated in vitro against three human cancer cell lines (BxPC-3, MCF-7, MDA-MB-231) and one normal cell line (hTERT-HPNE) using the MTT assay. Compound 4e showed the most potent cytotoxic activity against MDA-MB-231 (IC50 = 21.40 ± 1.22 µM), and compound 4c showed the most potent activity against BxPC-3 (IC50 = 26.17 ± 1.10 µM). Further investigation on BxPC-3 cells showed compound 4c induces apoptosis and cell cycle arrest at G0/G1 phase. The drug-likeness parameters of these oxadiazole derivatives were evaluated according to the Lipinski rule, the Veber rule, and Egan’s model. All of the derivatives were found to have good predicted absorption characteristics, with the exception of compound 4d due to its high lipophilicity.
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