Solvent free, microwave-assisted synthesis and cytotoxicity evaluation of benzoxazole derivatives

Abstract

Introduction: This work aims to develop an efficient green synthetic procedure and cytotoxicity evaluation of benzoxazole derivatives, an essential building block in medicinal chemistry research owing to its broad range of pharmacological properties, especially anticancer activity. Methods: The microwave-assisted condensation reaction between 2-amino-4-methylphenol and aromatic aldehydes using iodine as the oxidant under solvent-free conditions was explored. The cytotoxicity of the prepared benzoxazoles against the three human cancer cell lines including Lu-1, Hep-G2 and MCF-7 were examined using a MTT assay. Results: Five 2,5-disubstituted benzoxazole derivatives have been successfully synthesized in good yields (67-90%) using iodine as the oxidant under solvent-free microwave irradiation conditions. The initial cytotoxicity evaluation of the four synthesized compounds revealed that compounds 3b and 3e exhibited good activity against MCF-7 (IC50 = 12 μg/mL) and Hep-G2 (IC50 = 17.9 μg/mL), respectively. Remarkably, compound 3c showed the best cytotoxicity against MCF-7 at IC50 = 4 μg/mL. Conclusion: Microwave irradiation effectively assisted the condensation reaction between 2-amino-4-methylphenol and aromatic aldehydes in the presence of iodine under solvent-free conditions to facilitate the desired benzoxazoles in good total yields. The prepared benzoxazoles proved to be potent candidates for further study in the development of anticancer agents.