LC-DAD/MS/MS Detection of Macrocyclic Bisbibenzyls from the Liverwort Reboulia hemisphaerica and the Cell-based Screening of Their Microtubule Inhibitory Effects

Abstract

Aim To investigate the microtubule inhibitory active macrocyclic bisbibenzyls from the liverwort Reboulia hemisphaerica. Methods LC-DAD/MS/MS was used to detect macrocyclic bisbibenzyls from the microtubule depolymerization active extract of R. hemisphaerica. Preparative HPLC was applied for the isolation and purification of compounds, the structures of which were identified by spectroscopic technology. The antimicrotubule activities of these compounds were examined on human tumor cell line HeLa (cervical carcinoma) stably expressing EYFP-tubulin. Results Eleven bisbibenzyls were detected and eight of them were obtained and were further identified to be isomarchantin C ( 1), riccardin C ( 2), neomarchantin A ( 3), marchantin A ( 4), isoriccardin C ( 5), riccardin B ( 6), plagiochin E ( 7), and marchantin C ( 8). Compounds 4 and 8 showed strong microtubule depolymerization activities. Conclusion Compounds 3- 7 have been isolated from this plant for the first time. This is also the first report that bisbibenzyl is the novel class of natural molecule having antimicrotubule activity.