Viral infections affect several million patients annually.
Although
hundreds of viruses are known to be pathogenic, only a few can be
treated in the clinic with available antiviral drugs. Naturally based
pharmacotherapy may be a proper alternative for treating viral diseases.
Several natural and semisynthetic abietane-type diterpenoids have
shown important antiviral activities. In this study, a biological
evaluation of a number of either C-18- or C-19-functionalized known
semisynthetic abietanes against
Zika virus
,
Dengue virus
,
Herpes virus simplex
type
1, and
Chikungunya virus
are reported.
Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol
displayed broad-spectrum antiviral properties. The scale-up synthesis
of this analogue has been optimized for further studies and development.
This molecule displayed an EC
50
between 5.0 and 10.0 μM
against Colombian Zika virus strains and EC
50
= 9.8 μM
against Chikungunya virus. Knowing that this ferruginol analogue is
also active against
Dengue virus type
2 (EC
50
= 1.4 μM, DENV-2), we can conclude that this compound is a
promising broad-spectrum antiviral agent paving the way for the development
of novel antivirals.
The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 in the range 1.3–18.7 μM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents.
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