Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains

The treatment of benzylidenemalononitriles with phenylhydrazines in refluxing ethanol did not provide pyrazole derivatives, but instead furnished hydrazones. The structure of hydrazones was secured by X-ray analysis. The chemical proof was also obtained by direct reaction of 3,4,5-trimethoxybenzaldehyde with 2,4-dichlorophenylhydrazine. Newly synthesized hydrazones were tested against eight Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC₉₉). Five compounds were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)), with MIC₉₉ values ranging from 16 to 32 µg/mL and selective antifungal activity over cytotoxicity.