Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of Chikungunya virus replication
Autor(es): Bourjot Mélanie, Delang Leen, Nguyen Van Hung, Neyts Johan, Guéritte Françoise, Leyssen Pieter, Litaudon Marc
Resumo: A chemical study of the Vietnamese plant species Trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin A (1), along with several known coumarins - phenylpropanoids. The planar structure - the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1D- - 2D-NMR experiments, mass spectrometry, - comparison with literature data. Trigowiin A (1) exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound 1 is closely related to those of well-known tigliane diterpenoids such as prostratin (2), phorbol (3), 12-O-tetradecanoylphorbol 13-acetate (TPA) (4), - 4?-TPA (5), the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell-based assays of two additional members of the genus Alphavirus (Sindbis virus, SINV, - Semliki forest virus, SFV). Whereas prostratin inhibited CHIKV replication with a moderate EC(50) of 2.6 ?M - a selectivity index (SI) approximating 30, compound 4 proved to be an extremely potent inhibitor, with an EC(50) of ?3 nM - a SI near 2000. Interestingly, no or very little activity was observed on the replication of SINV - SFV.
Imprenta: Journal of Natural Products, v. 75, n. 12, p. 2183-2187, 2012
Identificador do objeto digital: 10.1021/np300637t
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya Virus - Virus
Data de publicação: 2012
