Biological activity of citridone A and its derivatives

      Citridone A (1), a potentiator of miconazole activity against Candida albicans, was originally isolated from the culture broth of Penicillium sp. FKI-1938.^1, Citridone A (1) has a rare phenyl-R-furopyridone skeleton (6-6/5/5 ring system) and 1 was the only natural compound having this ring system. Structurally related citridones B (2), C (3) and D (4) were also isolated from the fungus, but they showed very weak miconazole-potentiating activity. Because of its unique structure and biological properties, two groups have already completed its total synthesis.^{2, 3} These findings prompted us to synthesize new citridone A derivatives to understand the structure-activity relationship. Furthermore, the biological activity of the derivatives was re-evaluated in 15 in-house assay systems. Among 11 derivatives synthesized in this study, three derivatives, 17 (formyl 1), 20 (structural isomer of 1) and 21 (enantiomer of 1), potentiated miconazole activity against C. albicans. Interestingly, 1, 14 (demethyl 1), 20 and 21 were found to inhibit yellow pigment production in methicillin-resistant Staphylococcus aureus (MRSA).

   In this poster, we described the synthesis of citridone derivatives and their biological activity, including the potentiating activity of antifungal miconazole and inhibitory activity of yellow pigment production in MRSA.

1. Fukuda, T., et al. J. Antibiot. 58, 309-314 (2005)

2. Miyagawa, T., et al. Org. Lett. 13, 1158-1161 (2011)

3. Fotiadou, A-D. et al. Org. Lett. 13, 4592-4595 (2011)