RESUMO
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.
Assuntos
Vírus Chikungunya , Vírus , Infecção por Zika virus , Zika virus , Abietanos/farmacologia , Antivirais , Humanos , Replicação Viral , Infecção por Zika virus/tratamento farmacológicoRESUMO
Abietic acid (AA), dehydroabietic acid (DHA) and triptoquinones (TQs) are bioactive abietane-type diterpenoids, which are present in many edible vegetables and medicinal herbs with health-promoting properties. Evidence suggests that beneficial effects of diterpenes operate, at least in part, through effects on cells in the immune system. Dendritic cells (DCs) are a key type of leukocyte involved in the initiation and regulation of the immune/inflammatory response and natural or synthetic compounds that modulate DC functions could be potential anti-inflammatory/immunomodulatory agents. Herein, we report the screening of 23 known semisynthetic AA and DHA derivatives, and TQs, synthesized previously by us, in a multi-analyte DC-based assay that detects inhibition of pro-inflammatory cytokine production. Based on the magnitude of the inhibitory effect observed and the number of cytokines inhibited, a variety of activities among compounds were observed, ranging from inactive/weak to very potent inhibitors. Structurally, either alcohol or methyl ester substituents on ring A along with the introduction of aromaticity and oxidation in ring C in the abietane skeleton were found in compounds with higher inhibitory properties. Two DHA derivatives and two TQs exhibited a significant inhibition in all pro-inflammatory cytokines tested and were further investigated. The results confirmed their ability to inhibit, dose dependently, LPS-stimulated expression of the co-stimulatory molecules CD40 and/or CD86 and the production of the pro-inflammatory cytokines IL-1ß, IL-6, IL-12 and TNFα. Our results demonstrate that DC maturation process can be targeted by semisynthetic DHA derivatives and TQ epimers and indicate the potential of these compounds as optimizable anti-inflammatory/immunomodulatory agents.
Assuntos
Abietanos , Fator de Necrose Tumoral alfa , Abietanos/metabolismo , Abietanos/farmacologia , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Células Dendríticas , Ésteres/farmacologia , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.
Assuntos
Antraquinonas/química , Antivirais/química , Antivirais/farmacologia , Naftoquinonas/química , Animais , Linhagem Celular Tumoral , Chlorocebus aethiops , Vírus da Dengue/efeitos dos fármacos , Células HeLa , Herpesviridae/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Estrutura Molecular , Células VeroRESUMO
Combining antiviral drugs with different mechanisms of action can help prevent the development of resistance by attacking the infectious agent through multiple pathways. Additionally, by using faster and more economical screening methods, effective synergistic drug candidates can be rapidly identified, facilitating faster paths to clinical testing. In this work, a rapid method was standardized to identify possible synergisms from drug combinations. We analyzed the possible reduction in the antiviral effective concentration of drugs already approved by the FDA, such as ivermectin (IVM), ribavirin (RIBA), and acyclovir (ACV) against Zika virus (ZIKV), Chikungunya virus (CHIKV), and herpes virus type 2 (HHV-2). Essential oils (EOs) were also included in the study since they have been reported for more than a couple of decades to have broad-spectrum antiviral activity. We also continued studying the antiviral properties of one of our patented molecules with broad-spectrum antiviral activity, the ferruginol analog 18-(phthalimid-2-yl)ferruginol (phthFGL), which presented an IC99 of 25.6 µM for the three types of virus. In general, the combination of IVM, phthFGL, and oregano EO showed the greatest synergism potential against CHIKV, ZIKV, and HHV-2. For instance, this combination achieved reductions in the IC99 value of each component up to ~8-, ~27-, and ~12-fold for CHIKV, respectively. The ternary combination of RIBA, phthFGL, and oregano EO was slightly more efficient than the binary combination RIBA/phthFGL but much less efficient than IVM, phthFGL, and oregano EO, which indicates that IVM could contribute more to the differentiation of cell targets (for example via the inhibition of the host heterodimeric importin IMP α/ß1 complex) than ribavirin. Statistical analysis showed significant differences among the combination groups tested, especially in the HHV-2 and CHIKV models, with p = 0.0098. Additionally, phthFGL showed a good pharmacokinetic profile that should encourage future optimization studies.
RESUMO
Dengue virus (DENV) infection is the most arbovirosis in the world. However, medications have not been approved for its treatment. Drug discovery based on the host-targeted antiviral (HTA) constitutes a new promising strategy, considering their high genetic barrier to resistance and the low probability of selecting drug resistance strains. In this study, we have tested fifty-seven podophyllotoxin-related cyclolignans on DENV-2 infected cells and found the most promising compound was S.71. Using cellular and molecular biology experiments, we have discovered that the new lignan altered the distribution of microtubules, induced changes in cell morphology, and caused retraction of the rough endoplasmic reticulum. In addition, the compound alters the viral envelope protein and the double-stranded RNA, while there is a decrease in negative-strand RNA synthesis; especially when the compound was added between 6- and 12-hours post-infection. Altogether, S.71 decreases the viral yield through an HTA-related mechanism of action, possibly altering the DENV genome replication and/or polyprotein translation, through the alteration of microtubule distribution and endoplasmic reticulum deterioration. Finally, pharmacokinetic predictors show that S.71 falls within the standard ranges established for drugs.
Assuntos
Vírus da Dengue , Dengue , Viroses , Humanos , Vírus da Dengue/genética , Antivirais/uso terapêutico , Replicação Viral , Técnicas de Cultura de Células , Viroses/tratamento farmacológico , Dengue/tratamento farmacológicoRESUMO
Zika virus (ZIKV), a flavivirus that is mainly transmitted by A. aegypti and A. albopictus and sexual transmission, has been documented and described. The ZIKV RNA detection in the semen of vasectomized men indicates that accessory glands such as the prostate could be a site of virus replication. In this study, we characterized the ZIKV infection, evaluated the antiviral profile, and demonstrated the AXL and TIM-1 expression on the PC3 prostate cell line. It was also determined that PC3 cells are susceptible and permissive to ZIKV infection without altering the cell viability or causing a cytopathic effect. The antiviral profile suggests that the PC3 cells modulate the antiviral response through the suppressor molecule expression, SOCS-1, during a ZIKV infection.
RESUMO
BACKGROUND: The plants of the Asteraceae family have been used for medicinal purposes,in traditional Colombian medicine. AIM: To evaluate the antifungal activity and the cytotoxic effects of 15 essential oils from plants of the Asteraceae family. METHODS: Antifungal activity was evaluated against Candida parapsilosis ATCC 22019, Candida krusei ATCC 6258, Aspergillus flavus ATCC 204304 and Aspergillus fumigatus ATCC 204305 following EUCAST and CLSI M38-A standard methods, for yeast and filamentous fungi, respectively. Cytotoxic effect was evaluated on Vero cell line by MTT assay. RESULTS: The oils from the plants Achyrocline alata and Baccharislatifolia were the only ones active against A. fumigatus (GM-MIC=78.7 and 157.4 microg/ml, respectively). In contrast, there was no evidence of oils active against Candida species. In addition, these oils were not cytotoxic on Vero cells. The oils of A. alata and Baccharis latifolia could be candidates for disinfecting hospital environments and for inhibiting biofilm formation by A. fumigatus CONCLUSIONS: The oils of A. alata and B. latifolia could be candidates for disinfecting hospital environments and for inhibiting biofilm formation by A. fumigatus.
Assuntos
Achyrocline/química , Antifúngicos/isolamento & purificação , Aspergillus flavus/efeitos dos fármacos , Aspergillus fumigatus/efeitos dos fármacos , Baccharis/química , Candida/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Biofilmes/efeitos dos fármacos , Chlorocebus aethiops , Desinfetantes/isolamento & purificação , Desinfetantes/farmacologia , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/toxicidade , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/toxicidade , Células Vero/efeitos dos fármacosRESUMO
Two essential oils of Lippia alba (Mill.) N.E. Brown (Verbenacea), the carvone and citral chemotypes and 15 of their compounds were evaluated to determine cytotoxicity and antifungal activity. Cytotoxicity assays for both the citral and carvone chemotypes were carried out with tetrazolium-dye, which showed a dose-dependent cytotoxic effect against HeLa cells. Interestingly, this effect on the evaluated cells (HeLa and the non-tumoural cell line, Vero) was lower than that of commercial citral alone. Commercial citral showed the highest cytotoxic activity on HeLa cells. The antifungal activity was evaluated against Candida parapsilosis, Candida krusei, Aspergillus flavus and Aspergillus fumigatus strains following the standard protocols, Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing and CLSI M38-A. Results demonstrated that the most active essential oil was the citral chemotype, with geometric means-minimal inhibitory concentration (GM-MIC) values of 78.7 and 270.8 microg/mL for A. fumigatus and C. krusei, respectively. Commercial citral showed an antifungal activity similar to that of the citral chemotype (GM-MIC values of 62.5 microg/mL for A. fumigatus and 39.7 microg/mL for C. krusei). Although the citronellal and geraniol were found in lower concentrations in the citral chemotype, they had significant antifungal activity, with GM-MIC values of 49.6 microg/mL for C. krusei and 176.8 microg/mL for A. fumigatus.
Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Lippia/química , Monoterpenos/farmacologia , Monoterpenos Acíclicos , Antifúngicos/isolamento & purificação , Monoterpenos Cicloexânicos , Testes de Sensibilidade Microbiana , Monoterpenos/isolamento & purificação , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologiaRESUMO
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.
Assuntos
Acetona/química , Acetona/farmacologia , Antracenos/análise , Nitrogênio/química , Microbiologia do Solo , Poluentes do Solo/análise , Solo/análise , Dióxido de Carbono/análise , Concentração de Íons de Hidrogênio , México , Óxidos de Nitrogênio/análise , Fósforo/química , Compostos de Amônio Quaternário/análise , SolventesRESUMO
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.
Assuntos
Abietanos/química , Abietanos/síntese química , Abietanos/farmacologia , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Antivirais/síntese química , Podofilotoxina/análogos & derivados , Podofilotoxina/farmacologia , Animais , Antivirais/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Podofilotoxina/síntese química , Relação Estrutura-Atividade , Células VeroRESUMO
Six diterpenes isolated from the latex of Euphorbia obtusifolia Poir. (Euphorbiaceae) were evaluated for their inhibition of the NADH oxidase activity in submitochondrial particles from beef heart. 4,20-Dideoxyphorbol-12,13-bis(isobutyrate) was the most potent inhibitor and showed an inhibitory concentration with IC(50) value of 2.6+/-0.3mM. In the present study, some structure-activity trends are suggested for the inhibitory activity of the mammalian mitochondrial respiratory chain of these natural product derivatives of 4-deoxyphorbol esters.
Assuntos
Diterpenos/química , Diterpenos/farmacologia , Transporte de Elétrons/efeitos dos fármacos , Euphorbia/química , Látex/química , Mitocôndrias Cardíacas/metabolismo , Animais , Bovinos , Diterpenos/isolamento & purificação , Técnicas In Vitro , Mitocôndrias Cardíacas/efeitos dos fármacos , NADH NADPH Oxirredutases/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Rotenona/farmacologia , Desacopladores/farmacologiaRESUMO
The antifungal evaluation of twenty seven simple and heterocycle-fused prenyl-1,4-naphthoquinones and 1,4-anthracenediones was performed in vitro against human pathogenic yeasts (Candida spp.) and filamentous fungi (Aspergillus spp., Fusarium spp., and Trichophyton spp.). The synthetic strategy used to obtain the quinone derivatives was initially based on the Diels-Alder cycloaddition between myrcene and several p-benzoquinone derivatives, followed by cyclisation of the prenyl side chain in the case of anthracene-1,4-diones. The most promising compounds, displaying MIC values in the low µg/mL range, were those bearing one or two chlorine atoms attached to the quinone ring. Time-kill curves determined for the most potent compounds showed their fungistatic mode of action similar to that of itraconazole.
Assuntos
Antracenos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Naftoquinonas/farmacologia , Trichophyton/efeitos dos fármacos , Animais , Antracenos/síntese química , Antracenos/química , Antifúngicos/química , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Relação Estrutura-Atividade , Células VeroRESUMO
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.
Assuntos
Lagos , Hidrocarbonetos Policíclicos Aromáticos/química , Cloreto de Sódio/toxicidade , Solo/química , Tamaricaceae/efeitos dos fármacos , Dióxido de Carbono/metabolismo , Concentração de Íons de Hidrogênio , Cloreto de Sódio/química , Microbiologia do Solo , Poluentes do Solo/química , Tamaricaceae/crescimento & desenvolvimento , Fatores de TempoRESUMO
The syntheses of combretastatin A-4 from gallic acid and of three combretastatin-based hybrids are described. Starting from commercial gallic acid, the phosphonium salt (3,4,5-trimethoxybenzylphosphonium bromide) is synthesized and coupled, through a Wittig reaction, with several aldehydes, including methoxymethyl-protected isovanillin, the aldehyde y-bicyclohomofarnesal having a labdane skeleton, 3-(3-pyridyl) propanal, and furfural. The biological properties of the cis-coupled compounds as cytotoxic, antiviral and antifungal agents are also reported. In addition, pyrogallol, gallic and 3,4,5-trimethoxybenzoic acids have been studied biologically.
Assuntos
Antifúngicos/farmacologia , Antivirais/farmacologia , Estilbenos/síntese química , Estilbenos/farmacologia , Antifúngicos/química , Antivirais/química , Biologia MolecularRESUMO
A new bioactive diterpene skeleton resulting from a backbone rearrangement is described. Activity of the rearranged product and several derivatives against Herpes Virus Simplex type 2 is reported.
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Diterpenos/síntese química , Diterpenos/farmacologia , Herpesvirus Humano 2/efeitos dos fármacos , Animais , Chlorocebus aethiops , Concentração Inibidora 50 , Estrutura Molecular , Células Vero , Ensaio de Placa Viral , Replicação Viral/efeitos dos fármacosRESUMO
Labdadienedial and a series of C15,C16-functionalized derivatives were synthesized from commercial (+)-sclareolide and evaluated for their cytotoxic, antimycotic, and antiviral activities. Their precursors were similarly evaluated.
Assuntos
Diterpenos/síntese química , Diterpenos/farmacologia , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Antivirais/toxicidade , Chlorocebus aethiops , Diterpenos/química , Diterpenos/toxicidade , Fungos/efeitos dos fármacos , Células HeLa , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Células VeroRESUMO
A series of C18-oxygenated derivatives of dehydroabietic acid were synthesized from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities.
Assuntos
Abietanos/química , Abietanos/farmacologia , Abietanos/síntese química , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/síntese química , Antivirais/química , Antivirais/farmacologia , Linhagem Celular Tumoral , Fungos/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Concentração Inibidora 50 , Testes de Sensibilidade MicrobianaRESUMO
The synthesis of the marine natural products pyridinebetaine A and B is reported. The biological evaluation of pyridinebetaine A and B and several analogues as cytotoxic, antifungal and antiviral agents is also described. Unfortunately, none of the compounds tested showed relevant antifungal or cytotoxic activity. Only pyridinebetaine B reduced the Herpes simplex virus type 1 virus replication, though only weakly.
Assuntos
Alcaloides/síntese química , Alcaloides/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Betaína/síntese química , Betaína/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Alcaloides/química , Animais , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antivirais/química , Betaína/química , Chlorocebus aethiops , Fungos/efeitos dos fármacos , Células HeLa , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
A series of C18-oxygenated derivatives of abietic acid were synthesized and evaluated for their cytotoxic, antimycotic, and antiviral activities. In general, the introduction of an aldehyde group at C18 did improve the resultant bioactivity, while the presence of an acid or alcohol led to less active compounds.