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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
ResumoA 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.
ImprentaJournal of Natural Products, v. 75, n. 12, p. 2183-2187, 2012
Identificador do Objeto Digital10.1021/np300637t
DescritoresChikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya Virus - Virus
Data de Publicação:2012