Semisynthesis of Dolabellane Diterpenes: Oxygenated Analogues with Increased Activity against Zika and Chikungunya Viruses
Autor: | Freddy A. Ramos, Claudio Cesar Cirne-Santos, Jackson A. L. C. Resende, Ana Maria Viana Pinto, Caroline de Souza Barros, Maria Leonisa Sanchez Nunez, Izabel Christina Nunes de Palmer Paixão, Fabián Amaya García, Valéria Laneuville Teixeira, Leonardo Castellanos |
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Rok vydání: | 2021 |
Předmět: |
Stereochemistry
Pharmaceutical Science Epoxide Colombia medicine.disease_cause Antiviral Agents 01 natural sciences Analytical Chemistry chemistry.chemical_compound Chlorocebus aethiops Drug Discovery medicine Animals Chikungunya Vero Cells Pharmacology Molecular Structure biology 010405 organic chemistry Organic Chemistry Zika Virus Anthozoa biology.organism_classification Semisynthesis 0104 chemical sciences Oxygen Brown algae 010404 medicinal & biomolecular chemistry Caribbean Region Complementary and alternative medicine chemistry Vero cell Molecular Medicine Diterpenes Chikungunya virus |
Zdroj: | Journal of Natural Products. 84:1373-1384 |
ISSN: | 1520-6025 0163-3864 |
Popis: | Brown algae and soft corals represent the main marine sources of dolabellane diterpenes. The antiviral activity of dolabellanes has been studied for those isolated from algae, whereas dolabellanes isolated from soft corals have been barely studied. In this work, a collection of dolabellane diterpenes consisting of five natural and 21 semisynthetic derivatives was constructed, and their antiviral activities against Zika (ZIKV) and Chikungunya (CHIKV) viruses were tested. Dolabellatrienone (1) and (1R,7R,8R,11S)-7,8-epoxy-13-keto-dolabella-3,12(18)-diene (2), isolated from Eunicea genus soft corals, were employed to obtain 21 dolabellane and dolastane diterpenes by reactions such as allylic oxidations, reductions, acid-catalyzed epoxide ring opening, and acetylations. All of the compounds were identified by a combination of one- and two-dimensional NMR, mass spectrometry, and X-ray diffraction experiments. The cytotoxicites against Vero cells and the antiviral activities against ZIKV and CHIKV was tested to calculate the half-maximal effective concentration (EC50) and selectivity indexes (SIs). In general, the addition of oxygen-containing functional groups improved the bioactivity of dolabellane and dolastane diterpenes against ZIKV and CHIKV replication. Compound 9 showed an EC50 = 0.92 ± 0.08 μM and SI = 820 against ZIKV. |
Databáze: | OpenAIRE |
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