Antifungal macrocyclic bis(bibenzyls) from the Chinese liverwort Ptagiochasm intermedlum 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 µg 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.

Keywords:

• Ptagiochasm intermedlum L.
• Aytoniaceae
• macrocyclic bis(bibenzyls)
• riccardin C
• antifungal activity
• combined effect

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 30672531). We thank Dr Shu-juan Sun for the C. albicans strains, Dr Xue-sen Wen for plant identification, Ms Jian Ren and Dr Bin Ma for the NMR measurements, Dr Jie Xing and Ms Yan-hui Gao for the MS determination.