Synthesis of Some New 1,3,4-Oxadiazole Derivatives and Evaluation of Their Anticancer Activity.

In this work, some new 2-[(5-((2-acetamidophenoxy)methyl)-1,3,4-oxadiazol-2-yl)thio]acetamide derivatives () were synthesized and studied for their anticancer activity. Twelve new compounds were tested on the A549 human lung cancer cell line, C6 rat glioma cell line, and L929 murine fibroblast cell line. Compounds , and (IC: 1.59-7.48 μM), and especially (IC: <0.14 μM), exhibited excellent cytotoxic profile on A549 with selectivity. Compounds and showed remarkable antiproliferative activity on the C6 cell line with IC values of 8.16 and 13.04 μM, respectively. The compounds with the lowest IC value on the A549 cell line (, and ) were further studied to determine the mechanism of action. These compounds were found to induce apoptosis with a higher ratio (16.10-21.54%) than that of the standard drug cisplatin (10.07%). Compound displayed mitochondrial membrane depolarization and caspase-3 activation at most, whereas compounds (89.66%) and (78.78%) had outstanding retention rates in the G0/G1phase of the cell cycle (cisplatin 74.75%). Compounds , and exhibited matrix metalloproteinase-9 (MMP-9) inhibition higher than 75% at 100 μg/mL; even IC values were found to be 1.65 and 2.55 μM for and . In addition, physicochemical properties of the compounds and molecular docking interaction of compound on the MMP-9 enzyme were evaluated; the desired and expected results were obtained.