Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids.

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 EC50 between 5.0 and 10.0 µM against Colombian Zika virus strains and EC50 = 9.8 µM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC50 = 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.

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

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.

Enhanced dissipation of polycyclic aromatic hydrocarbons in the rhizosphere of the Athel tamarisk (Tamarix aphylla L. Karst.) grown in saline-alkaline soils of the former lake Texcoco.

Remediation of polycyclic aromatic hydrocarbons (PAHs) contaminated alkaline saline soil with phreatophyte or "water loving plants" was investigated by spiking soil from the former lake Texcoco with 100 mg phenanthrene (Phen) kg(-1) soil, 120 mg anthracene (Ant)kg(-1) soil and 45 mg benzo(a)pyrene (BaP) kg(-1) soil and vegetating it with Athel tamarisk (Tamarix aphylla L Karst.). The growth of the Athel tamarisk was not affected by the PAHs. In soil cultivated with Athel tamarisk, the leaching of PAHs to the 32-34 cm layer decreased 2-fold compared to the uncultivated soil. The BaP concentration decreased to 39% of the initial concentration at a distance smaller than 3 cm from the roots and to 45% at a distance larger than 3cm, but 59% remained in unvegetated soil after 240 days. Dissipation of Ant and Phen decreased with depth, but not BaP. The biodegradation of PAHs was affected by their chemical properties and increased in the presence of T. aphylla, but decreased with depth.

Using acetone as solvent to study removal of anthracene in soil inhibits microbial activity and alters nitrogen dynamics.

Acetone is often used as a carrier to contaminate soil with polycyclic aromatic hydrocarbons (PAHs) and then to study the factors that control their removal. Acetone is an organic solvent that might affect soil processes. An alkaline saline (Texcoco soil) and an agricultural soil (Acolman soil) were amended with or without acetone, nitrogen + phosphorus (NP), and contaminated with anthracene at 520 mg/kg soil while emissions of CO2 and N2O and concentrations of NH4+, NO2(-) and NO3(-) were monitored. The CO2 emission rate decreased greater than 10 times in the soils amended with acetone. Emission of N2O decreased 70 times in the Acolman soil amended with acetone and NP and 5 times in the Texcoco soil. The concentration of NH4+ decreased in the unamended Acolman and Texcoco soil but increased when acetone was added in the first and remained constant in the latter. Acetone inhibited the increase in the amount of NO3(-) in the Acolman soil but not in the Texcoco soil. It was found that microbial activity as evidenced by the emission of CO2, nitrification, and production of N2O were inhibited by acetone. The amount of acetone used as solvent should thus be kept to a minimum, but it can be assumed that its effect on soil processes will be temporary, as microorganisms are known to repopulate soil quickly.

Synthesis, cytotoxicity and antiviral activity of podophyllotoxin analogues modified in the E-ring.

Several podophyllotoxin derivatives modified in the E-ring were prepared and evaluated for their cytotoxicity on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28) and for their antiherpetic activity against Herpes simplex virus type II. The trimethoxyphenyl moiety was oxidized to ortho-quinone and further condensed with diamines and enamines to form different heterocycles. Most of the compounds maintained their cytotoxicity at the muM level and some of them showed antiherpetic activity.