Docking, Synthesis, Antifungal and Cytotoxic Activities of Some Novel Substituted 4H-Benzoxazin-3-one

Abstract

A series of some novel 4H-benzoxazin-3-one derivative (1a-20a) was designed, synthesized and evaluated as antifungal and anticancer agents. Benzoxazine compounds were synthesized in only two steps. In the first step, o-aminophenols derivatives reacted with chloroacetyl chloride in the presence of K2CO3 to produce a 4H-benzoxazin-3-one intermediate. In the second step, this intermediate was reacted to various alkyl or aryl halides to get the final products. Then, the synthetic benzoxazine compounds were evaluated for their antifungal activity against different species of fungi. Compound 13a MICs GM of 28.5 µg/mL and then compounds 14a, 17a with MICs GM of 47.2 and 50.7 µg/mL demonstrated the most excellent inhibitory activities against Candida strains, respectively. In addition, the potential cytotoxic activities of all compounds were evaluated by two methods: MTT test, and also lactate dehydrogenase test (LDH). According to the biological results, the most of our compounds especially those containing benzyl groups on the nitrogen atom showed significant antifungal activity. Cytotoxic activities of the compounds were also determined on Hep-G2 and SW cell lines by MTT method and LDH. In MTT assay, compounds 5a, 6a and 8a showed the best results (IC50: 3.12 µg/mL) followed by compounds 7a, 13a and 17a (IC50: 6.25 µg/mL) on the Hep-G2 cells. The best cytotoxic compounds against SW cells were 17a and 18a. The LDH assay showed the same results with MTT of SW.