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.