Biswulfenioidins A-E, dioxygen-bridged abietane-type diterpenoid dimers with anti-Zika virus potential from Orthosiphon wulfenioides

By:Tu, Wen-Chao ; Huang, Yong-Xiang ; Kong, Yuan-Lin ; Li, Bo ; Wang, Bin-Bao ; Dong, Tian-Hao ; Chen, Wei-Chi ; Zeb, Muhammad Aurang ; Li, Xiao-Li ; Liu, Mei-Feng ; Zheng, Chang-Bo ; Xiao, Wei-Lie

Organic Chemistry Frontiers

DOI：https://doi.org/10.1039/d4qo00619d

Published：2024-MAY

Abstract

      Five novel abietane-type diterpenoid dimers (ADDs), biswulfenioidins A-E (1-5), one known bisditerpenoid (6), and two possible precursors (7 and 8) were isolated from O. wulfenioides. Their structures were determined and characterized by X-ray diffraction, quantum chemical calculations, and extensive spectroscopic methods. Compounds 1-4 were unprecedented 6-O-12 ' and 7-O-11 ' angular fused dioxygen-bridged ADDs, while 5 and 6 were rare 6-O-7 ' and 7-O-6 ' parallel fused. Putative biosynthetic pathways of 1-6 were proposed. Interestingly, possible precursors 7 and 8 showed high cytotoxic effects, while dimerized diterpenoids 1-6 exhibited negligible cytotoxicity against Vero cells. Compounds 5 and 6 showed potent activity against Zika virus (ZIKV) superior to the positive drug ribavirin. Western blot and immunofluorescence experiments exhibited that 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) and NS5 protein.