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

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.

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.

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.

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.