Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds

Background and purpose: Oxadiazole-derived compounds have been shown to have a wide range of pharmacological activities. 2, 5-Disubstituted 1, 3, 4-oxadiazole derivatives have occupied a specific place in the design of anti-proliferative agents. In the present work a series of 2, 5-disubstituted 1, 3, 4-oxadiazoles derivatives containing amide group has been synthesized via a two-step reaction. Experimental approach: A mixture of substituted carboxylic acid derivatives, semicarbazide, and phosphorus oxychloride in reflux condition yielded 2-amino-5-aryl-1, 3, 4-oxadiazole derivatives. Acylation of the amino group of the resultant oxadiazole with 6-chloronicotinoyl chloride in dry tetrahydrofuran/pyridine afforded the final products. The synthesized molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase domain (PDB: 1M17) crystal structure to study the possible interactions with the active site. Cytotoxic activities of final products against HeLa and MCF-7 cells were also assessed by MTT assay. Findings/Results: Compounds IIb, IIc, and IIe had a considerable cytotoxic activity with IC50 values of 19.9, 35, and 25.1 µM, respectively against HeLa cells. The highest docking score was -7.89 kcal/mol for compound IIe. Conclusion and implications: Compound IIe exhibited remarkable cytotoxic activity against the two tested cell lines particularly HeLa cells which was in accordance with the in silico ΔG bind result but further evaluations are necessary to prove these findings.