Antifungal macrocyclic <i>bis</i>(bibenzyls) from the Chinese liverwort <i>Ptagiochasm intermedlum</i> L.

Abstract

Six macrocyclic bis(bibenzyls) were obtained from the Chinese liverwort Ptagiochasm intermedlum L., and their structures were elucidated as pakyonol (1), neomarchantin A (2), isoriccardin C (3), marchantin H (4), riccardin F (5) and riccardin C (6) on the basis of spectroscopic data and comparison with known compounds. Among them, compounds 3-5 were isolated from this liverwort species for the first time. They possessed in vitro antifungal properties against the fluconazole-sensitive and resistant strains of Candida albicans, with minimum inhibitory concentrations (MICs) ranging from 32 to >512 microg mL(-1). Furthermore, riccardin C was also demonstrated to act as a fungal resistance modifying agent when its combined effect with fluconazole on three resistant strains of C. albicans was investigated. The synergistic or additive activity of riccardin C caused dramatically reduced MICs of fluconazole by at most 256-fold.