RESUMO
The search for new compounds with biocidal potential was carried out, focusing on the longipinenes 1-7 from the plant species Santolina viscosa Lag. Compounds 1, 2, and 5 showed remarkable molecular diversity when treated in acidic reaction conditions. Protonic, Lewis, and heterogeneous compounds were used in the treatment. Three main models of reaction have been observed: isomerization of the double bond (8-10); rearrangements to longibornane-based skeleton (11-15) and ring-opening to himachalane-based skeleton (16-18). Secolongibornane aldehydes 23 and 24 were obtained after epoxide opening under the same reaction conditions. The elucidation of the structures of the new compounds was carried out using spectroscopic data and was supported by computational theoretical calculations of 13C NMR spectra. Additionally, high-resolution mass spectrometry and single-crystal X-ray diffraction analysis were employed for certain compounds. Natural longipinenes 4-7, methyl esters 1-3 of corresponding natural carboxylic acids and the isomerized and derivatives compounds 8-19 exhibit moderate to high insecticidal activity against R. padi and M. persicae insects. Longipinene 5 shows potent inhibition against the root growth of the plants L. perenne and L. sativa, as well as compound 2 on the leaves of L. perenne. Furthermore, significant ixocidal and nematicidal activity was found for this latter compound.
Assuntos
Inseticidas , Animais , Inseticidas/química , Inseticidas/farmacologia , Catálise , Estrutura Molecular , Norbornanos/química , Norbornanos/farmacologiaRESUMO
Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinson's Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms. Some BPHs have selectively inhibited MAO-B, with IC50 values ranging from sub-nM to µM. The most potent compound with IC50 = 0.6 nM was the 3',4'-dichloro-BPH 16, which showed highly selective and reversible MAO-B inhibitory activity. Furthermore, the most selective BPHs displayed a significant protection against the apoptosis, and mitochondrial toxic effects induced by 6-hydroxydopamine (6OHDA) on SH-SY5Y cells, used as a cellular model of PD. The results of virtual binding studies on the most potent compounds docked in MAO-B and MAO-A were in agreement with the potencies and selectivity indexes found experimentally. Additionally, related to toxicity risks, drug-likeness and ADME properties, the predictions found for the most relevant BPHs in this research were within those ranges established for drug candidates.
Assuntos
Neuroblastoma , Doença de Parkinson , Estilbenos , Humanos , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/química , Doença de Parkinson/tratamento farmacológico , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacologia , Relação Estrutura-Atividade , Compostos de Benzil/síntese química , Compostos de Benzil/química , Compostos de Benzil/farmacologiaRESUMO
This article describes the structure revision of nine triterpenoids that have been reported corresponding to the same 13C NMR data set. In addition, 13C NMR calculation shows that some chemical shift assignments must be swapped. Our analysis improves the fit between the experimental and calculated data. Correcting misassigned structures and correctly assigning each signal is essential for elucidating new structurally related compounds. Furthermore, the ambiguity of several compounds, the structure of which differs in the literature and the Sci-Finder database, has been eliminated. Misassigned structures were found by chemical shift searches in NAPROC-13, and the results provide two or more different compounds with the same 13C NMR data. The process to determine the correct, most likely structural proposal in agreement with the experimental 13C NMR data was carried out by DFT calculations.
Assuntos
Produtos Biológicos , Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Teoria da Densidade Funcional , Estrutura MolecularRESUMO
A considerable number of natural products have been published in recent years with misassigned structure, even though they had been correctly elucidated in the past. The availability of databases containing revised structures can prevent the amplification of errors in structural elucidation. NAPROC-13, a dereplication tool based on the 13C chemical shift, has been used to search for substances that, possessing the same chemical shifts, have been described with different structures. The correct structure of these different structural proposals is verified by computational chemistry. This paper reports the structural revision of nine triterpenoids following this methodology.
Assuntos
Produtos Biológicos , Produtos Biológicos/química , Bases de Dados Factuais , Estrutura MolecularRESUMO
A novel DFT-based Reaction Kinetics (DFT-RK) simulation approach, employed in combination with real-time data from reaction monitoring instrumentation (like UV-vis, FTIR, Raman, and 2D NMR benchtop spectrometers), is shown to provide a detailed methodology for the analysis and design of complex synthetic chemistry schemes. As an example, it is applied to the opening of epoxides by titanocene in THF, a catalytic system with abundant experimental data available. Through a DFT-RK analysis of real-time IR data, we have developed a comprehensive mechanistic model that opens new perspectives to understand previous experiments. Although derived specifically from the opening of epoxides, the prediction capabilities of the model, built on elementary reactions, together with its practical side (reaction kinetics simulations of real experimental conditions) make it a useful simulation tool for the design of new experiments, as well as for the conception and development of improved versions of the reagents. From the perspective of the methodology employed, because both the computational (DFT-RK) and the experimental (spectroscopic data) components can follow the time evolution of several species simultaneously, it is expected to provide a helpful tool for the study of complex systems in synthetic chemistry.
RESUMO
A detailed experimental and theoretical study corroborates that the reductive deoxygenation of activated (allylic or benzylic) alcohols with excess Ti(III) proceeds via an allyl(benzyl)-radical and allyl(benzyl)-Ti, which is protonated, regioselectively in the case of allylic derivatives. The H atom of the newly formed C-H bond in the product originates from the -OH group of the starting material. The deoxygenation of lithium alkoxides or alcohols by using 1.0 mol of Ti(III) leads to the corresponding dimerization products in good yields. An excellent agreement with the experimental data was obtained by using a reaction kinetics simulator to discriminate between competing reactions.
Assuntos
Álcoois/química , Compostos Organometálicos/química , Oxigênio/química , Teoria Quântica , Titânio/química , Dimerização , Radicais Livres/química , Estrutura Molecular , OxirreduçãoRESUMO
We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC50 values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.
Assuntos
Fármacos Anti-HIV/farmacologia , Cumarínicos/farmacologia , HIV-1/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Fármacos Anti-HIV/síntese química , Linhagem Celular , Cumarínicos/síntese química , Genes Reporter , HIV-1/fisiologia , Células HeLa , Humanos , Concentração Inibidora 50 , Luciferases/biossíntese , Luciferases/genética , NF-kappa B/antagonistas & inibidores , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/antagonistas & inibidoresRESUMO
Several pinacol derivatives of podophyllotoxins bearing different side chains and functions at C-7 were synthesized through reductive cross-coupling of podophyllotoxone and several aldehydes and ketones. While possessing a hydroxylated chain at C-7, the compounds retained their respective hydroxyl group with either the 7α (podo) or 7ß (epipodo) configuration. Along with pinacols, some C-7 alkylidene and C-7 alkyl derivatives were also prepared. Cytotoxicities against neoplastic cells followed by cell cycle arrest and cellular microtubule disruption were evaluated and mechanistically characterized through tubulin polymerization inhibition and assays of binding to the colchicine site. Compounds of the epipodopinacol (7ß-OH) series behaved similarly to podophyllotoxin in all the assays and proved to be the most potent inhibitors. Significantly, 7α-isopropyl-7-deoxypodophyllotoxin (20), without any hydroxyl function, appeared as a promising lead compound for a novel type of tubulin polymerization inhibitors. Experimental results were in overall agreement with modeling and docking studies performed on representative compounds of each series.
Assuntos
Antimitóticos/síntese química , Antineoplásicos/síntese química , Podofilotoxina/análogos & derivados , Podofilotoxina/síntese química , Antimitóticos/farmacologia , Antineoplásicos/farmacologia , Ligação Competitiva , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Microtúbulos/efeitos dos fármacos , Microtúbulos/ultraestrutura , Modelos Moleculares , Podofilotoxina/farmacologia , Estereoisomerismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/farmacologiaRESUMO
The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC(50) values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.
Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Isoindóis/química , Isoindóis/síntese química , Isoindóis/farmacologia , Animais , Antimaláricos/uso terapêutico , Antimaláricos/toxicidade , Benzeno/química , Linhagem Celular , Imidazóis/uso terapêutico , Imidazóis/toxicidade , Concentração Inibidora 50 , Isoindóis/uso terapêutico , Isoindóis/toxicidade , Masculino , Camundongos , Parasitemia/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/patogenicidade , Plasmodium falciparum/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia obtusifolia (Cecropiaceae) and Psychotria poeppigiana (Synonym: Cephaelis elata, Rubiaceae) are two Latin American plants broadly used in traditional Amerindian medicine. The former, together with many other species of the genus Cecropia, share the folk reputation of curing heart failure, cough, asthma and bronchitis. The latter is used in Panama by Kuna and Ngäbe Buglé (Guaymies) native Indians for the treatment of dyspnea. AIM OF THE STUDY: Based on screening of selected medicinal Panamanian plants by radioligand-binding techniques by Caballero-George et al. (2001), the present study was carried out in order to investigate the vasoactive effects of different fractions from both P. poeppigiana and C. obtusifolia on rat thoracic aorta and identify active fractions and their chemical constituents. MATERIALS AND METHODS: Both acid and neutral methanol fractions (P-AMeOH and P-NMeOH) and acid and neutral dichlorometane fractions (P-ADCM and P-NDCM) were obtained from P. poeppigiana crude methanolic and dichlorometane extracts, respectively. Identical fractionation was carried out for C. obtusifolia (C-AMeOH, C-NMeOH, C-ADCM and C-NDCM. Vasorelaxant effect of all fractions, and their inhibition of contractile responses to angiotensin II were evaluated in isolated aortic rings. RESULTS: P-AMeOH, P-NMeOH and P-ADCM fractions induced a concentration-dependent relaxation (43.9+/-1.8%, 35.3+/-4.7% and 52.9+/-3.5%, respectively) in the endothelium-intact aorta precontracted by phenylephrine (PE, 10(-6)M). The relaxation produced by C-AMeOH and C-NMeOH (57.3+/-2.5% and 53.3+/-3.3%, respectively) was greater than the effect produced by C-ADCM and C-NDCM (42.2+/-3.4% and 21.8+/-0.8%, respectively). Only the incubation of the aortic rings with P-AMeOH reduced the maximum contraction induced by angiotensin II at 20.08+/-0.55%. CONCLUSIONS: The direct vasorelaxation effect observed could explain in part the ethnomedical use of these plants in Amerindian traditional medicine. The most active fractions contain phenolic and aromatic acid compounds. Furthermore, P-AMeOH, the only fraction that showed both vasorelaxant effect and inhibition of contractile responses to angiotensin II, is the most rich in aromatic acids compounds and the only one that contains scopoletin.
Assuntos
Cecropia/química , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Psychotria/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Angiotensina II/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Etnofarmacologia , Humanos , Indígenas Centro-Americanos , Masculino , Medicina Tradicional , Panamá , Componentes Aéreos da Planta , Extratos Vegetais/química , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Vasoconstritores/farmacologiaRESUMO
Fifteen dihydrosphingosine analogues have been synthesized and tested in vitro against Mycobacterium tuberculosis (MTB). Two ether (3 and 4b) and one diamine (8b) derivatives have displayed high mycobactericidal potency, with similar MIC values of 1.25 microg/mL, against the virulent strain H37Rv, as well as against a clinical isolate resistant to the five first-line anti-TB drugs. The three compounds, tested on other eleven cultured MTB strains with different multi-drug-resistance (MDR) patterns, retained their MIC values for most strains, or even lowered it, as in the case of compound 4b, which, assayed on strain No. 332, also resistant to all first-line anti-TB drugs, attained the MIC value of 0.78 microg/mL.
Assuntos
Antibacterianos/química , Mycobacterium tuberculosis/efeitos dos fármacos , Esfingosina/análogos & derivados , Antibacterianos/síntese química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Esfingosina/síntese química , Esfingosina/química , Esfingosina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Dimerocostus strobilaceus is used by the Kuna Indians of Panama for the treatment of hypertension and other cardiovascular diseases. AIM OF THE STUDY: We investigated the vascular effects of acid and neutral fractions obtained from methanol and dichloromethane extracts of Dimerocostus strobilaceus. MATERIALS AND METHODS: The acid and neutral methanol fractions (A-MeOH and N-MeOH) or acid and neutral dichlorometanic fractions (A-DCM and N-DCM) were tested using isolated rat aortic rings with or without endothelium pre-contracted by phenylephrine. We examined the ability of these different fractions at different concentrations to modify vascular responses induced by angiotensin II using endothelium-denuded aortic rings from Spontaneously Hypertensive Rats (SHR). RESULTS: In aortic rings with intact endothelium A-MeOH, N-MeOH and A-DCM fractions produced a concentration-dependent vasorelaxation (62.4 +/- 5.2, 64.5 +/- 5.0 and 63.7 +/- 5.0%, respectively), whereas the N-DCM fraction did not produce any vasorelaxant effect. Maximal relaxation evocated by vasoactive fractions was substantially inhibited on aortic rings without endothelium.Our study demonstrates that A-MeOH, N-MeOH, A-DCM and N-DCM significantly reduce contractile responses induced by angiotensin-II on aortic rings. CONCLUSIONS: Our findings may contribute to a better understanding of the potential link between vascular properties observed with Dimerocostus strobilaceus and their ethnobotanical use.
Assuntos
Endotélio/efeitos dos fármacos , Magnoliopsida , Extratos Vegetais/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Angiotensina II , Animais , Aorta , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Masculino , Panamá , Fenilefrina , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Vasoconstritores/farmacologiaRESUMO
Bioassay-guided fractionation of the dichloromethane extract of the leaves of Marila pluricostata led to the isolation of 2alpha,3beta-dihydroxy-D:A-friedoolean-28-oic acid (pluricostatic acid), a new friedelane triterpenoid, (1), ten known triterpenoids and three sterols. Their chemical structures were elucidated through spectroscopic analysis. The less polar fractions, on GC/MS analysis and comparison with a MS library, resulted in the identification of twenty four sesquiterpenoids. The new triterpenoid acid 1 showed cytotoxicity against the MCF-7, H-460, and SF-268 human cancer cell lines with GI(50) values from 1.2 to 3.3 microg/mL.
Assuntos
Clusiaceae/química , Folhas de Planta/química , Triterpenos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Modelos Moleculares , Triterpenos/química , Triterpenos/farmacologiaRESUMO
A number of aminoalcohols, diamines and other related cycloanalogues of sphingosine have been synthesized and assayed in vitro against three Leishmania spp. and Trypanosoma cruzi. Most of the compounds were potent parasiticides, with IC50 values in the microM or lower range and potencies higher than those of pentamidine and benznidazol, the common therapeutic agents against these parasitoses.
Assuntos
Cicloexanóis/farmacologia , Leishmania/efeitos dos fármacos , Esfingosina/análogos & derivados , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cicloexanos/síntese química , Cicloexanos/química , Cicloexanos/farmacologia , Cicloexanóis/síntese química , Cicloexanóis/química , Diaminas/síntese química , Diaminas/química , Diaminas/farmacologia , Concentração Inibidora 50 , Esfingosina/farmacologia , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/químicaRESUMO
Anxiolytic-like effects induced on mice by several compounds with imidazo[2,1-a]isoindolol (II), pyrimido[2,1-a]isoindolol (III) and [1,3]diazepino[2,1-a]isoindolol (IV) structures have been evaluated through the elevated plus-maze test. The evaluation has been based on measuring the spent time and counting the number of entries of mice in the open arms of the maze. Single intraperitoneal administration of imidazoisoindolol IIe and pyrimidoisoindolols IIIa, IIIe and IIIg induced significant increments in these behavioural parameters.
Assuntos
Ansiolíticos/farmacologia , Indóis/farmacologia , Animais , Ansiolíticos/química , Indóis/química , Aprendizagem em Labirinto , Camundongos , Modelos Moleculares , Relação Estrutura-AtividadeRESUMO
[reaction: see text] A general method for the one-step regioselective synthesis of 1-alkyl- or 1-aryl-1H-indazoles from ortho-halogenated alkanoylphenones, benzophenones, and arylcarboxylic acids, via copper-catalyzed amination, was developed by using 0.2% mol of CuO in the presence of K(2)CO(3). The reaction involves amination followed by intramolecular dehydration. Different functionalized alkyl aryl ketones, diaryl ketones, and benzoic acid derivatives were efficiently coupled with several hydrazines. Ligands commonly employed as catalysts for intermolecular amination were shown to be ineffective for this cyclization.
Assuntos
Aldeídos/química , Ácidos Carboxílicos/química , Cobre/química , Hidrocarbonetos Halogenados/química , Indazóis/síntese química , Cetonas/química , Alquilação , Aminação , Derivados de Benzeno/síntese química , Benzoatos/química , Carbonatos/química , Catálise , Ciclização , Hidrazinas/química , Hidrocarbonetos Aromáticos , Ligantes , Modelos Químicos , Potássio/químicaRESUMO
Lymphoproliferation inhibition and cytotoxicity of a number of lipidic aminoacids, aminoalcohols and diamines were evaluated as a preliminary screening to select potential immunomodulators. The four most potent/less toxic compounds were submitted to delayed hypersensibility (DTH) assays to define the best to be evaluated further Graft-vs-Host, NO production and other immunoevaluation (CD4(+), CD45, CD8, CD11b, I-Ek, and NK cells) assays, to establish their immunomodulation potential for being further considered as auxiliary agents for vaccination against some parasitic infections. Compounds 5d, 6d, 6f, 7a, and 9a, fairly inhibited the lymphoproliferation (71.6-79.5%, at 3.2-2.4 nM), while the aminoalcohol derivative 6f and the diamine 7a gave the most promising results in the DTH assays. Diamine derivative 8b induced nitrite production on normal macrophages, whereas compounds 6f and 7a induced nitrite production on LPS pre-stimulated macrophages. These two last compounds have been selected to follow in vivo vaccination assays.
Assuntos
Amino Álcoois/química , Amino Álcoois/farmacologia , Diaminas/química , Diaminas/farmacologia , Fatores Imunológicos/síntese química , Fatores Imunológicos/farmacologia , Amino Álcoois/síntese química , Amino Álcoois/toxicidade , Proliferação de Células/efeitos dos fármacos , Diaminas/síntese química , Diaminas/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Fatores Imunológicos/química , Fatores Imunológicos/toxicidade , Estrutura Molecular , Nitritos/metabolismo , Relação Estrutura-AtividadeRESUMO
Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-kappaB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalazinone, imidazoindole and pyrimidoisoindole derivatives are tested for their anti-HIV activity. Original assays based on recombinant viruses were used to evaluate HIV replication inhibition and stably transfected cell lines were used to evaluate inhibition of Tat and NF-kappaB proteins. Some of the stilbene-related heterocyclic compounds analysed displayed anti-HIV activity through interference with NF-kappaB and Tat function. Moreover, compounds inhibiting both targets displayed a stronger activity on viral replication.
Assuntos
Fármacos Anti-HIV/farmacologia , Compostos Heterocíclicos/farmacologia , Estilbenos/farmacologia , Produtos do Gene tat/antagonistas & inibidores , Repetição Terminal Longa de HIV , Células HeLa , Humanos , NF-kappa B/antagonistas & inibidoresRESUMO
Bioassay-guided fractionation of the chloroform and ethanol extracts of Tovomita longifolia leaves using cytotoxic and antimicrobial assays resulted in the isolation of four new benzophenones, (E)-3-(2-hydroxy-7-methyl-3-methyleneoct-6-enyl)-2,4,6-trihydroxybenzophenone (1), (E)-3-(6-hydroxy-3,7-dimethylocta-2,7-dienyl)-2,4,6-trihydroxybenzophenone (2), 8-benzoyl-2-(4-methylpenten-3-yl)chromane-3,5,7-triol (3), and 5-benzoyl-1,1,4a-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-xanthene-6,8-diol (4), and two known benzophenones, 4-geranyloxy-2,6-dihydroxybenzophenone (5) and 3-geranyl-2,4,6-trihydroxybenzophenone (6). The structures of 1-4 were established by spectroscopic means and by molecular modeling calculations. Compounds 1 and 3-5 demonstrated cytotoxic activities against breast (MCF-7), central nervous system (SF-268), and lung (H-460) human cancer cell lines, while compounds 3-6 showed antimicrobial activity against Klebsiella pneumoniae, Mycobacterium smegmatis, Pseudomonas aeruginosa, Salmonella gallinarum, and Staphylococcus aureus.
Assuntos
Antibacterianos , Antineoplásicos Fitogênicos , Benzofenonas , Clusiaceae/química , Plantas Medicinais/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Benzofenonas/química , Benzofenonas/isolamento & purificação , Benzofenonas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium smegmatis/efeitos dos fármacos , Panamá , Folhas de Planta/química , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
We have evaluated the anti-HIV activity of eleven natural 4-phenylcoumarins isolated from Marila pluricostata and three of their derivatives. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibitions of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Most of the coumarins tested displayed NF-kappaB inhibition. Two coumarins were also Tat antagonists and the presence of both activities correlated with a stronger inhibition of HIV replication. Our results show that antiviral effect of 4-phenylcoumarins can be related to the inhibition of NF-kappaB and Tat, and suggest that these types of compounds can be useful in the treatment of HIV infection as viral transcription inhibitors.