Bioinspired benzoxanthene lignans as a new class of antimycotic agents: synthesis and Candida spp. growth inhibition

In this work we synthetized the bioinspired benzoxanthene lignans (BXLs) 3, 14-22, and the phenazine derivative 23 as potential antimycotic agents. MICs and MFCs against Candida strains were determined. In a preliminary screening, compounds 3, 15, 20, 21, 22 were substantially inactive. Compounds 14 and 17 showed antifungal activity, being able to inhibit the growth of the majority of Candida strains with MIC values in the range 4.6-19.2 µM (14) and 26.0-104.3 µM (17); for three strains, the MICs were lower than those obtained using the antimycotic drug fluconazole. The three BXLs 18, 19 and 23 showed some MIC values lower than that of fluconazole; 18 was also active against two non-albicans Candida strains resistant to fluconazole. Phenazine 23, although active only against one strain (MIC = 1.3 µM), was one order of magnitude more potent than fluconazole. All the BXLs were fungicidal.