Anti-herpetic and anti-dengue activity of abietane ferruginol analogues synthesized from (+)-dehydroabietylamine

Abstract

The abietane-type diterpenoid (+)-ferruginol (1), a bioactive compound isolated from several plants, has attracted much attention as consequence of its pharmacological properties, which includes antibacterial, antifungal, antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and antitumor actions. In this study, we report on the antiviral evaluation of ferruginol (1) and several analogues synthesized from commercial (+)-dehydroabietylamine. Thus, the activity against Human Herpesvirus type 1, Human Herpesvirus type 2 and Dengue Virus type 2, was studied. Two ferruginol analogues showed high antiviral selectivity index and reduced viral plaque-size in post-infection stages against both Herpes and Dengue viruses. A promising lead, compound 8, was ten-fold more potent (EC50 = 1.4 μM) than the control ribavirin against Dengue Virus type 2. Our findings suggest that the 12-hydroxyabieta-8,11,13-triene skeleton, which is characteristic of the diterpenoid ferruginol (1), is an interesting molecular scaffold for development of novel antivirals. In addition, the cytotoxic and antifungal activities of the synthesized ferruginol analogues have also been investigated. (©)20155 Elsevier Science. All rights reserved.

Diterpenes as lead molecules against neglected tropical diseases

“…Triptolide (0.5–4 ng/mL) is reported to decrease the expression of nuclear factor‐kappa B and activate protein‐1 expression along with cyclooxygenase‐2 and prostaglandin E‐2 production in dengue virus‐infected, human lung, liver, and dendritic cells (Liou et al ., ). Cyclopaldic acid, sphaeropsidin A (Cimmino et al ., ), 12‐hydroxyabieta‐8,11,13‐triene skeleton diterpenoid, ferruginol (Roa‐Linares et al , ), and diterpenes from Copaifera reticulata (Geris et al ., ) and Trigonostemon cherrieri (Allard et al ., ) are found to act against A. aegypti . Additionally, diterpenoids from C. reticulata caused the death of A. aegypti larvae by cell destruction in the midgut (Valotto et al , ).…”

Antiproliferative Activity and Effect on GABAA Receptors of Callitrisic Acid Derivatives

“…The ready availability of these materials from our studies (4b-5) and the absence of their biological studies as well as chemical manipulation prompted us to carry out this research. Thus, in continuation of our research program to discover bioactive terpenoids [10][11][12][13], we carried out the synthesis of several derivatives of methyl callitrisate (4b), including callitrisic acid (4a), jiadifenoic acid C (5), and 4-epidehydroabietol or callitrisinol (6) together with an evaluation of their antiproliferative and modulating GABA A receptor activities. Herein, the evaluation of compounds 1-6 against a panel of six representative human solid tumor cell lines and their effect on GABA A receptors (α 1 β 2 γ 2s ) are reported.…”

Diterpenes and their derivatives as promising agents against dengue virus and dengue vectors: A literature‐based review

“…In a similar fashion, a phenolic derivative of (+)‐ferruginol and 18‐oxoferruginol exhibited anti‐DENV effects (EC 50 values 1.4 and 5.0 μM, respectively) against DENV serotype 2 (Roa‐Linares et al, ). In the same context, andrographolide (10 mg/kg (i.p.)…”