Synthesis and antiproliferative activity of aryl- and heteroaryl-hydrazones derived from xanthone carbaldehydes.

In order to explore the antiproliferative effect associated with the xanthone framework, several arylhydrazonomethyl derivatives were synthesized from various isomeric 1,3-dihydroxyxanthone carbaldehydes. Variation in the position of the aldehydic function led to three sets of compounds, bearing the hydrazonomethyl chain at positions 5, 6 or 7 on the xanthone nucleus, respectively. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against two human cancer cell lines (MCF-7, breast adenocarcinoma, and KB 3.1, squamous cell oral carcinoma) for two time periods (24 h and 72 h). Among the series, four compounds exhibited interesting growth inhibitory effects against both the cell lines, with IC(50) values in the micromolar concentration range. When compared with doxorubicin, the xanthone derivatives showed moderate cytotoxic effects. Surprisingly, unlike doxorubicin, these compounds displayed no significant time-dependent change in the concentration causing 50% inhibitory effect in proliferation. This unusual cytotoxicity profile led to the hypothesis that these molecules could be endowed with a mechanism of action distinct to that of doxorubicin.

(2-Arylhydrazonomethyl)-substituted xanthones as antimycotics: synthesis and fungistatic activity against Candida species.

A series of arylhydrazones derived from various 6,8-diacetoxy- or 6,8-dihydroxy-9-oxo-9H-xanthene carboxaldehydes were synthesized and evaluated for their in vitro antifungal properties against two human pathogenic yeasts (Candida albicans and C. krusei) according to a diffusion method. The activity was strongly dependent from the position of the (1-arylhydrazinyl-2-ylidene)methyl chain in the xanthone molecular skeleton. Compounds having the nitrogen side chain in the 4-position, with a further halogen substitution on the terminal phenyl ring showed fungistatic effects. Within this series, the 4-fluorophenylhydrazinyl derivative 13g exhibited the highest activity, particularly against C. krusei, with a greater efficacy than that of econazole, used as reference.