Lichen Xanthones as Models for New Antifungal Agents.

Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for new antimicrobial compounds plays an important role in current medicinal chemistry research. Inspired by lichen antimicrobial xanthones, a series of novel chlorinated xanthones was prepared using five chlorination methods (Methods A⁻E) to obtain different patterns of substitution in the xanthone scaffold. All the synthesized compounds were evaluated for their antimicrobial activity. Among them, 3-chloro-4,6-dimethoxy-1-methyl-9-xanthen-9-one showed promising antibacterial activity against (ATCC 29212 and 29213) and ATCC 29213. 2,7-Dichloro-3,4,6-trimethoxy-1-methyl-9-xanthen-9-one revealed a potent fungistatic and fungicidal activity against dermatophytes clinical strains (, , and (MIC = 4⁻8 µg/mL)). Moreover, when evaluated for its synergistic effect for , compound exhibited synergy with fluconazole (ΣFIC = 0.289). These results disclosed new hit xanthones for both antibacterial and antifungal activity.