RESUMO
Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI50 values ranging between 5.3 (±0.32) and 14 (±0.90) µM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15−19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI50 values ranging between 12 (±1.5) and 17 (±1.1) µM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC50 values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.
Assuntos
Antineoplásicos , Sesquiterpenos , Trypanosoma cruzi , Animais , Antineoplásicos/farmacologia , Células HeLa , Humanos , Camundongos , Sesquiterpenos/farmacologia , Relação Estrutura-AtividadeRESUMO
DNA polymerases are enzymes that play a crucial role in DNA metabolism such as replication, repair, transcription, recombination, and chromosome segregation during mitosis. Herein we report the isolation of a new iridoid (6-epi-catalpol, 2) and per-O-acetyl-verbascoside (11) from aerial part of Buddleja cordobensis Grisebach (Buddlejaceae). From compound 2, we have obtained eight compounds by chemical transformation. This group of compounds at a concentration of 500µM was assayed against Taq DNA polymerase. Compound 11 (per-O-acetyl-verbascoside) was the most active with an IC50 of 1.21±0.18µM; compounds 9, 2 and 8 were strong inhibitors with IC50 values of 5.57±0.70, 21.62±0.22 and 78.13±0.93µM, respectively. Compounds 11 and 9 could be a leader structures to development new anticancer chemotherapy medicines and a useful tool to investigate DNA polymerase activity.
Assuntos
Inibidores Enzimáticos/farmacologia , Glucosídeos/farmacologia , Fenóis/farmacologia , Taq Polimerase/antagonistas & inibidores , Concentração Inibidora 50RESUMO
Two semisynthetic acetyl derivatives of the alkaloid sauroine from Huperzia saururus, monoacetyl sauroine, and diacetyl sauroine (DAS) were obtained and their chemical structures were analyzed by NMR. While monoacetyl sauroine is the typical product of acetylation, DAS is an unexpected derivative related to the keto-enol formation of sauroine. Recordings of field excitatory post-synaptic potentials from the CA1 region of rat hippocampal slices showed that only DAS acutely applied induced chemical long-term potentiation (LTP) in a dose-dependent manner with an EC50 of 1.15 ± 0.09 µM. This effect was blocked by 10 µM D(-)-2-amino-5-phosphonopentanoic acid (AP5), suggesting dependence on the NMDA receptor. DAS significantly increased NMDA receptor-dependent excitatory post-synaptic currents without affecting α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor-dependent currents. Repetitive administration of DAS improved visuo-spatial learning in the Morris Water Maze. In slices from rats tested in the Morris Water Maze, LTP resulting from electrical synaptic stimulation was 2.5 times larger than in controls. Concentration of DAS measured in the brain after repetitive administration was 29.5 µM. We conclude that slices perfused with DAS display a robust NMDA receptor-dependent chemical LTP. During chronic treatment, DAS enhances learning abilities through a metaplastic mechanism as revealed by the augmentation of LTP in slices. DAS, therefore, may be a promising compound as a nootropic therapeutic drug. A semisynthetic derivative of sauroine, diacetyl sauroine (DAS), induces chemical long-term potentiation in rat hippocampal slices increasing the NMDA receptor-dependent current. 2 mg/kg prior to each session in a Morris Water Maze (MWM) improves behavior performance. In slices prepared from the tested rats the electrical stimulation-dependent long-term potentiation (LTP) was greatly enhanced. Therefore, DAS may have potency as a nootropic drug against the memory decline.
Assuntos
Alcaloides/farmacologia , Hipocampo/efeitos dos fármacos , Huperzia/química , Potenciação de Longa Duração/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Nootrópicos , Alcaloides/farmacocinética , Animais , Encéfalo/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Região CA3 Hipocampal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Plasticidade Neuronal/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Relação Estrutura-Atividade , Sinapses/efeitos dos fármacosRESUMO
RATIONALE: Sauroxine and N-demethylsauroxine are lycodine-type Lycopodium alkaloids. In recent years, Lycopodium alkaloids have gained significant interest due to their unique skeletal characteristics as well as due to their acetylcholinesterase activity. It is known that drugs that inhibit acetylcholinesterase can be used to treat the early stages of Alzheimer's disease. METHODS: Sauroxine and N-demethylsauroxine were isolated from the aerial parts of Huperzia saururus (Lam.) Trevis. Electron ionization mass spectrometry (EI-MS) (low resolution) and collision-induced dissociation tandem mass spectrometry (CID-MS/MS) fragmentation was conducted using an ion trap, GCQ Plus mass spectrometer with MS/MS. Electron ionization high-resolution mass spectrometry (EI-HRMS) was performed in a magnetic sector mass spectrometer (Micromass VG). RESULTS: Using GC/EI-CID-MS/MS we obtained different fragmentation routes that connect all the ionic populations. In addition, the use of EI-HRMS allowed us to measure the exact masses of all the fragment ions, and, with all this information gathered, we tried to establish a fragmentation scheme concordant with the ascendant and descendant species. CONCLUSIONS: The mass spectrometry studies presented in this work complete our mass studies of Lycopodium alkaloids. The mass spectrometry work presented has been very useful to confirm the structures as well as to support the biogenetic relationships between the lycodine-type Lycopodium alkaloids: sauroxine and N-demethylsauroxine.
Assuntos
Alcaloides/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Lycopodium/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Íons/química , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodosRESUMO
Coumarin derivatives were prepared using natural products isolated from plants belonging in the Pterocaulon genus (Asteraceae) and commercial drugs. Some molecules have displayed interesting activity against myeloid murine leukemia virus-reverse transcriptase (MMLV-RT) (compounds 20 and 28 produced inhibition with IC50 values of 38.62 and 50.98 µM, respectively) and Taq DNA polymerase (analogues 13 and 14 produced inhibition with IC50 values of 48.08 and 57.88 µM, respectively). Such inhibitors may have importance as antiretroviral chemotherapeutic agents and also in the development of anticancer drugs.
Assuntos
Cumarínicos/química , Cumarínicos/farmacologia , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia , Taq Polimerase/antagonistas & inibidores , Animais , Asteraceae/química , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Concentração Inibidora 50 , Camundongos , Modelos Biológicos , Estrutura Molecular , Vírus da Leucemia Murina de Moloney/enzimologia , Preparações de Plantas/química , Inibidores da Transcriptase Reversa/síntese químicaRESUMO
In order to determine the existence of synergism, the bacteriostatic action of flavonoids against Escherichia coli ATCC 25 922 between dihydroxylated chalcones and a clinically interesting conventional antibiotic, binary combinations of 2',3-dihydroxychalcone, 2',4-dihydroxychalcone and 2',4'-dihydroxychalcone with nalidixic acid and its ternary combinations with rutin (inactive flavonoid) were assayed against this Gram negative bacterium. Using a kinetic-turbidimetric method, growth kinetics were monitored in broths containing variable amounts of dihydroxychalcone alone, combinations of dihydroxychalcone variable concentration-nalidixic acid constant concentration and dihydroxychalcone variable concentration-nalidixic acid constant concentration-rutin constant concentration, respectively. The minimum inhibitory concentrations of dihydroxychalcones alone and its binary and ternary combinations were evaluated. All chalcones, and their binary and ternary combinations showed antibacterial activity, being rutin an excellent synergizing for the dihydroxychalcone-nalidixic acid binary combination against E. coli ATCC 25 922. Thus, this synergistic effect is an important way that could lead to the development of new combination antibiotics against infections caused by E. coli.
RESUMO
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed alpha-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38-1.86muM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G(1) phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Glucosídeos/química , Glucosídeos/farmacologia , Iridoides/química , Iridoides/farmacologia , Anexina A5/metabolismo , Antineoplásicos/síntese química , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores Enzimáticos/metabolismo , Glucosídeos/síntese química , Humanos , Glucosídeos Iridoides , Iridoides/síntese química , Modelos Moleculares , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
A series of analogs were synthesized in a straightforward manner from naturally available sesquiterpenes ilicic acid and tessaric acid. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D and WiDr. The most potent analog induced considerably growth inhibition in the range 1.9-4.5 microM. Cell cycle studies for tessaric acid derivatives indicated a prominent arrest of the cell cycle at the G(2)/M phase. Damage to the cells was permanent as determine by the so called 24+24 drug schedule.
Assuntos
Antineoplásicos/química , Sesquiterpenos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Divisão Celular , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Fase G2 , Humanos , Neoplasias/tratamento farmacológico , Relação Quantitativa Estrutura-Atividade , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologiaRESUMO
In this paper, the effects of 3 natural sesquiterpene lactones, i.e., helenalin (Hln), mexicanin (Mxc), and dehydroleucodine (DhL), were evaluated using cultured Leishmania mexicana promastigotes. It was observed that the compounds inhibited the in vitro growth of the parasites at relatively low concentrations. The effect was rapid and irreversible with an estimated IC50 of 2-4 microM, while all the lactones were more effective than ketoconazole. Moreover, these compounds exhibited low cytotoxicity for mammalian cells. Hln induced strong vacuolization of the parasite cytoplasm, although pericellular microtubules were preserved. The 3 lactones induced DNA fragmentation as judged by the high labeling with the fluorescent TUNEL method, which was confirmed by electrophoresis on agarose gels. The ability of the parasites to invade Vero cells was also decreased by exposure to low concentrations of the compounds. We conclude that these compounds can affect the parasite's life cycle, possibly through multiple mechanisms. Identification of the molecular targets of these natural products and their effects on amastigotes should be determined to evaluate the possible therapeutic use of the compounds against leishmaniasis.
Assuntos
Antiprotozoários/farmacologia , Lactonas/farmacologia , Leishmania mexicana/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Artemisia/química , Asteraceae/química , Chlorocebus aethiops , Fragmentação do DNA , DNA de Protozoário/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Leishmania mexicana/genética , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/ultraestrutura , Microscopia Eletrônica de Transmissão , Sesquiterpenos de Guaiano , Células VeroRESUMO
Secondary metabolites play a major role in the adaptation of plants to the environment. Furan neo-clerodane diterpenes are characteristic secondary metabolites in Baccharis flabellata Hook. & Arn. var. flabellata. One of the main compounds is the diene ent-15,16-epoxy-19-hydroxy-1,3,13(16),14-clerodatetraen-18-oic acid (DAC). In this work a new dimeric compound (DACD) has been isolated and identified by NMR and MS techniques. The presence of other minor dimers was also observed in the same plant methanolic extracts. Assuming that they may be the products of [4â¯+â¯2] condensation of two monomeric moieties, the formation of adducts by photochemical dimerization was checked by inducing the in vitro [4â¯+â¯2] cycloaddition of DAC. Moreover, the DAC and DACD accumulation rates in aerial parts of B. flabellata specimens were analyzed monthly during a complete phenological cycle. The accumulation of monomer depends on the plant phonological stage; meanwhile the dimer proportion arises in detriment of the monomer as the solar UV radiation increases. Since plants exposed to strong UV intensities produce radical species, the scavenger properties of these compounds toward reactive nitrogen species (RNS), and reactive oxygen species (ROS), were analyzed. Albeit DAC and DACD show significant superoxide radical scavenger activities, the monomer proved to be more effective than the dimer toward ROS, while DACD was an excellent RNS scavenger.
Assuntos
Baccharis/química , Diterpenos Clerodânicos/química , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Oxigênio/química , Raios Ultravioleta , Baccharis/metabolismo , Reação de Cicloadição , Dimerização , Sequestradores de Radicais Livres/química , Espectroscopia de Ressonância Magnética , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/químicaRESUMO
In order to establish structure-activity relationships, nine neo-clerodane diterpenes isolated from the acetone extract of aerial parts of Baccharis flabellata Hook & Arn var. fabellata were assayed for antifeedant activity against Tribolium castaneum (Coleoptera: Tenebrionidae). Compounds exhibiting maximal antifeedant activities showed an alpha,beta-unsaturated carbonyl group on the decalin portion and a furan ring at the side chain. Stereoelectronic studies indicate that the distance between the furan heteroatom and the more electrophilic carbon of the decaline moiety, as well as the electrostatic charge on that atom, were important features for antifeedant activity. Compounds possesing an alpha,beta,gamma,delta-unsaturated carbonyl group or an acetoxyl group at C-2, were inactive. Theoretical calculations were performed in order to find some structure-activity relationships.
Assuntos
Baccharis/química , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Tribolium/efeitos dos fármacos , Animais , Diterpenos Clerodânicos/isolamento & purificação , Comportamento Alimentar/efeitos dos fármacos , Conformação Molecular , Ressonância Magnética Nuclear Biomolecular , Rotação Ocular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Tribolium/fisiologiaRESUMO
Flavonoids have attracted great interest due to their possible anticancer activities. Here we investigated the antiproliferative activity of the flavonoids isolated from Baccharis scandens against human leukemia cell lines and found that the methoxyflavonoid gardenin B was the most cytotoxic compound against HL-60 and U-937 cells, showing IC50 values between 1.6 and 3.0 µM, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. These effects on viability were accompanied by the concentration- and time-dependent appearance of apoptosis as evidenced by DNA fragmentation, formation of apoptotic bodies and a sub-G1 ratio increase. Comparative studies with the best-studied bioflavonoid quercetin indicate that gardenin B is a more cytotoxic and more apoptotic inducer than quercetin. Cell death induced by gardenin B was associated with: (i) a significant induction of caspase-2, -3, -8 and -9 activities; (ii) cleavage of the initiator caspases (caspase-2, -8 and -9), of the executioner caspase-3, and of poly(ADP-ribose) polymerase; and (iii) a concentration-dependent reactive oxygen species generation. In conclusion, apoptosis induced by gardenin B is associated with activation of both the extrinsic and the intrinsic apoptotic pathways of cell death and occurs through a mechanism that is independent of the generation of reactive oxygen species.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Flavonas/farmacologia , Leucemia/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos Fitogênicos/química , Baccharis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flavonas/química , Células HL-60 , Humanos , Leucemia/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismoRESUMO
Sesquiterpene lactones constitute a large group of biologically active compounds obtained from plants. The lactones, mexicanin (MXN) and helenalin (HLN), were reported recently as active against the infective form of Trypanosoma cruzi. In this work, we studied the effects of these compounds on the growth and viability of the noninfective epimastigote, to compare the sensitivity of the 2 stages and to characterize their actions. Both compounds were cytotoxic to the parasites, with HLN (inhibitory concentration 50% [IC50] 1.9 +/- 0.08 microM) more potent than MXN (IC50 3.8 +/- 0.19 microM) and the typanocidal drug, benznidazole (IC50 8.6 +/- 2.5 microM). The results showed that epimastigotes are less sensitive than trypomastigotes to the compounds. The trypanocidal effect of these lactones, irreversible after 12-hr exposure, was not reversed by the reducing agents dithiotreitol or beta-mercaptoethanol. Ultrastructurally, we observed cytoplasmic vacuolization and nuclear disorganization. Although concentrations between 0.5 and 1.5 microM of the drugs were not lethal to the parasites, epimastigotes became thinner and their nuclei became more pycnotic after exposure. We conclude that MXN and HLN are deleterious for T. cruzi epimastigotes and that their mechanism of action is different than that of the related lactone, dehydroleucodine.
Assuntos
Lactonas/farmacologia , Sesquiterpenos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Asteraceae/química , Microscopia Eletrônica , Nitroimidazóis/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Sesquiterpenos de Guaiano , Trypanosoma cruzi/ultraestruturaRESUMO
The preventive effect of natural xanthanolides as well as a series of synthetic derivatives on ulcer formation induced by absolute ethanol in rats was examined. Among the compounds tested, xanthatin gave the strongest protective activity. The inhibitory action exerted by this molecule on the lesions induced by 0.6N HCl and 0.2N NaOH was highly significant, reducing ulceration in the range of 58-96% at a dose from 12.5 to 100mg/kg. These results appear to confirm that the presence of a non-hindered alpha,beta-unsaturated carbonyl group seems to be an essential structural requirement for the gastric cytoprotective activity of these compounds. In order to explore this possibility, a theoretical conformational analysis was performed. We suggest that the mechanism of protection would involve, at least in part, a nucleophylic attack of the sulfhydryl group from the biological molecules present in the gastric mucosa to electrophylic carbons accessible in suitable Michael acceptors.
Assuntos
Antiulcerosos/farmacologia , Sesquiterpenos/farmacologia , Xanthium/química , Animais , Antiulcerosos/química , Depressores do Sistema Nervoso Central , Fenômenos Químicos , Físico-Química , Etanol , Ácido Clorídrico , Espectroscopia de Ressonância Magnética , Masculino , Modelos Moleculares , Conformação Molecular , Método de Monte Carlo , Extratos Vegetais/química , Ratos , Ratos Wistar , Sesquiterpenos/química , Hidróxido de Sódio , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Relação Estrutura-AtividadeRESUMO
Allelochemical effects were observed when Tribolium castaneum (Herbst) adults were treated with Baccharis salicifolia (Ruiz & Pavon) Pers essential oil. The main biological activities were toxicity and repellence. Terpenes present in the essential oil were identified by GC-MS, and some authentic samples were tested to assess their activity individually. The most acutely toxic compounds after 3 days were beta-pinene and pulegone. Most of the monoterpenes elicited symptoms indicative of neurotoxicity. The most repellent compound was alpha-terpineol. Toxic and repellent effects of chemical derivatives of the major sesquiterpene present in B salicifolia essential oil, as well as a series of monoterpenes, were evaluated in order to investigate structure-activity relationships. The reduced derivatives of the monoterpenes and sesquiterpenes were more repellent that their carbonyl analogues. In addition, unsaturation in the germacrane skeleton enhanced repellent activity.
Assuntos
Baccharis/química , Repelentes de Insetos , Inseticidas , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Tribolium/fisiologia , Animais , Estrutura Molecular , Monoterpenos/química , Monoterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
To validate the potential as added-value resources of Asteraceae and Labiatae species of Argentinean semi-arid lands, we have selected 13 of their major terpenoids belonging to several chemical classes and tested their insect antifeedant and toxic activity on the herbivorous insects Spodoptera littoralis and Leptinotarsa decemlineata. The antifeedant effects of the test compounds were structure- and species-dependent. The most active antifeedant to L. decemlineata was the eudesmane sesquiterpene gamma-costic acid (13), followed by the labdane diterpene 2alpha,3alpha-dihydroxycativic acid (8), the clerodane diterpenes 6-acetylteucjaponin B (5), bacchotricuneatin A (1), bartemidiolide (7), butanolide (4), and the sesquiterpenes ilicic acid (11) and tessaric acid (10) (eudesmane and eremophilane type, respectively). S. littoralis was only affected by the clerodanes and showed the strongest response to salviarin (3) and 5, followed by hawtriwaic acid (6) and 12-epi-bacchotricuneatin A (2). Orally injected S. littoralis larvae were negatively affected by 5. Most of the diterpenes had selective cytotoxic effects to insect-derived Sf9 cells with the clerodane 1 being the most active, followed by the eudesmane costic acid (12), the only cytotoxic sesquiterpene. None of these compounds was cytotoxic to mammalian CHO cells.
Assuntos
Asteraceae/química , Lamiaceae/química , Sesquiterpenos/química , Terpenos/química , Ração Animal , Animais , Anti-Infecciosos , Argentina , Asteraceae/classificação , Asteraceae/parasitologia , Clima Desértico , Insetos/patogenicidade , Lamiaceae/classificação , Lamiaceae/parasitologia , Doenças das Plantas/parasitologia , Sesquiterpenos/toxicidade , Spodoptera/efeitos dos fármacos , Spodoptera/patogenicidade , Terpenos/toxicidadeRESUMO
Two clerodane-type diterpene glycosides esters, which were studied as peracetyl derivatives, together with the known diterpene marrubiagenine, were isolated from the aerial part of Baccharis sagittalis (Less). Their structures were established by spectroscopic methods. Antifeedant activity toward Tenebrio molitor larvae of the isolated compounds along with six other diterpenes was evaluated and some structure-antifeedant bioactivity relationships are reported.
Assuntos
Baccharis/química , Diterpenos Clerodânicos , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Inseticidas/isolamento & purificação , Inseticidas/farmacologia , Animais , Comportamento Alimentar/efeitos dos fármacos , Inseticidas/química , Larva/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Componentes Aéreos da Planta/química , Tenebrio/efeitos dos fármacosRESUMO
Synthetic coumarins were prepared in high yields using ionic liquids as an environmental friendly alternative. 3,4-Dimethyl-7-hydroxycoumarin (3ab) and 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (3bc) showed interesting activity against Taq DNA polymerase with IC50 values of 115.7 microM and 82.2 microM, respectively. Also, 4-methyl-7-hydroxycoumarin (3aa) and 4-methyl-5,7-dihydroxycoumarin (3ba) exhibited inhibitory activity against MMLV-RT with IC50 values of 23.5 microM and 18.3 microM, respectively. These inhibitors could have importance as antiretroviral chemotherapeutic agents and also for the development of antitumor drugs.
Assuntos
Cumarínicos/síntese química , Inibidores Enzimáticos/síntese química , Extratos Vegetais/síntese química , Cumarínicos/química , Cumarínicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Taq Polimerase/antagonistas & inibidoresRESUMO
Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host's cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes. We first observed that the antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of the compounds, suggesting that lactones may react with intracellular sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, significantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these findings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act by another mechanism.
RESUMO
INTRODUCTION: The aim of the present study was to analyze the larvicidal activity of different crude extracts of Larrea cuneifolia and its most abundant lignan, nordihydroguaiaretic acid (NDGA), against Culex quinquefasciatus. METHODS: Chloroform, methanol, and aqueous extracts from L. cuneifolia and NDGA were tested against larvae of Cx. quinquefasciatus under laboratory conditions. RESULTS: The chloroform extract showed the highest larvicidal effect, with an estimated LC50 of 0.062 mg/ml. NDGA also demonstrated significant larvicidal activity with an estimated LC50 of 0.092 mg/ml. CONCLUSIONS: These results indicate that the chloroform extract of L. cuneifolia and NDGA are promising insecticides of botanical origin that could be useful for controlling Cx. quinquefasciatus.