3,4-seco-Prenyllabdane sesterterpenoids and 3,4-seco-labdane diterpenoids with Zika virus inhibitory potential from Callicarpa nudiflora

Abstract

Two rearranged prenyllabdane sesterterpenoids nudiflorawus A-B (1-2) with a previously unreported carbon skeleton, and five undescribed 3,4-seco-labdane diterpenoids, nudiflorawus C-G (3-7), along with two known diterpenoids (8-9), were isolated from the leaves of Callicarpa nudiflora. Compounds 1-2 exhibited the first example of 3,4-seco-prenyllabdane sesterterpenoids with a unique six-membered ring in the side chain. Their structures were established via various spectroscopic methods. NMR calculations with DP4+ analysis and ECD were further adopted to confirm their relative and absolute configurations. Compound 6 showed significant Zika virus (ZIKV) inhibitory activity with an EC₅₀ value of 25.35 ± 0.742 μM. Western blot, quantitative real-time PCR, and immunofluorescence results further indicated that compound 6 could block ZIKV infection and replication by inhibiting the expression of ZIKV-envelope protein.

Keywords: Anti-ZIKV activity; Callicarpa nudiflora; Diterpenoid; Labdane; Lamiaceae; Sesterterpenoid.