RESUMO
Antiviral compounds targeting viral replicative processes have been studied as an alternative for the control of begomoviruses. Previously, we have reported that the peptide AmPep1 has strong affinity binding to the replication origin sequence of tomato yellow leaf curl virus (TYLCV). In this study, we describe the mechanism of action of this peptide as a novel alternative for control of plant-infecting DNA viruses. When AmPep1 was applied exogenously to tomato and Nicotiana benthamiana plants infected with TYLCV, a decrease in the synthesis of the two viral DNA strands (CS and VS) was observed, with a consequent delay in the development of disease progress in treated plants. The chemical mechanism of action of AmPep1 was deduced using Raman spectroscopy and molecular modeling showing the formation of chemical interactions such as H bonds and electrostatic interactions and the formation of π-π interactions between both biomolecules contributing to tampering with the viral replication.
Assuntos
Amaranthus/química , Antivirais/química , Antivirais/farmacologia , Begomovirus/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , RNA Viral/química , Replicação Viral/efeitos dos fármacos , Begomovirus/química , Begomovirus/genética , Begomovirus/fisiologia , Sequências Repetidas Invertidas/efeitos dos fármacos , Solanum lycopersicum/virologia , Doenças das Plantas/virologia , Proteínas de Plantas/química , RNA Viral/genética , Nicotiana/virologiaRESUMO
We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.
Assuntos
Complexos de Coordenação/química , Cobre/química , Animais , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Relação Dose-Resposta a Droga , Ligantes , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ratos , Análise EspectralRESUMO
The multidrug resistance (MDR) phenotype is considered as a major cause of the failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the overexpression of drug efflux pumps of a P-glycoprotein. The development of compounds that mitigate the MDR phenotype by modulating the activity of these transport proteins is an important yet elusive target. Here, we screened the saponification and enzymatic degradation products from Salvia hispanica seed's mucilage to discover modulating compounds of the acquired resistance to chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was used to purify the hydrolysis degradation products. All compounds were tested in eight different cancer cell lines and Vero cells. All compounds were noncytotoxic at the concentration tested against the drug-sensitive and multidrug-resistant cells (IC50 > 29.2 µM). For the all products, a moderate vinblastine-enhancing activity from 4.55-fold to 6.82-fold was observed. That could be significant from a therapeutic perspective. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Oligossacarídeos/farmacologia , Mucilagem Vegetal/química , Salvia/química , Vimblastina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Chlorocebus aethiops , Humanos , Sementes/química , Células VeroRESUMO
Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named retro-curcuminoids (7-14), was synthesized and characterized using 1D ¹H- and 13C-NMR, IR, and mass spectrometry; the X-ray structure of 7, 8, 9, 10, 12, 13, and 14 are reported here for the first time. The main structural feature of these compounds is the reverse linkage of the two aromatic moieties, where the acid chloride moiety is linked to the phenolic group while preserving α, ß-unsaturated ketone functionality. The cytotoxic screening of 7, 8, 9, and 10 at 50 and 10 µg/mL was carried out with human cancer cell lines K562, MCF-7, and SKLU-1. Lipid peroxidation on rat brain was also tested for compounds 7 and 10. Compounds 7, 8, and 10 showed relevant cytotoxic activity against these cancer cell lines, and 10 showed a protective effect against lipid peroxidation. The molecular resemblance to curcuminoids and analogs with ortho substituents suggests a potential source of useful bioactive compounds.
Assuntos
Antineoplásicos , Curcumina/análogos & derivados , Estirenos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ácidos Cumáricos/química , Cristalografia por Raios X , Humanos , Células MCF-7 , Masculino , Ressonância Magnética Nuclear Biomolecular , Ratos , Ratos WistarRESUMO
Antimicrobial peptides (AMPs) constitute an important alternative in the search for new treatments against pathogens. We analyzed the sequence variability in cytokine and chemokine proteins to investigate whether these molecules contain a sequence useful in the development of new AMPs. Cluster analysis allowed the identification of tracts, grouped in five categories showing structure and sequence homology. The structure and function relationship among these groups, was analyzed using physicochemical parameters such as length, sequence, charge, hydrophobicity and helicity, which allowed the selection of a candidate that could constitute an AMP. This peptide comprises the C-terminal alpha-helix of chemokines CXCL4/PF-457-70. Far-UV CD spectroscopy showed that this molecule adopts a random conformation in aqueous solution and the addition of 2, 2, 2 trifluoroethanol (TFE) is required to induce a helical secondary structure. The CXCL4/PF-457-70 peptide was found to have antimicrobial activity and very limited hemolytic activity. The mechanism of action was analyzed using model kinetics and molecular dynamics. The kinetic model led to a reasonable assumption about a rate constant and regulatory step on its mechanism of action. Using molecular dynamics simulations, the structural properties the CXCL4/PF-457-70 have been examined in a membrane environment. Our results show that this peptide has a strong preference for binding to the lipid head groups, consequently, increasing the surface density and decreasing the lateral mobility of the lipids alters its functionality.
Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Dicroísmo Circular , Análise por Conglomerados , Bases de Dados de Proteínas , Eritrócitos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fluoresceínas/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Cinética , Simulação de Dinâmica Molecular , Fator Plaquetário 4/química , Engenharia de Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Análise de Sequência de ProteínaRESUMO
The alkylation reaction of 2,2'-diseleno and 4,4'-diseleno-bis(benzoic acid) derivatives in the presence of sodium borohydride and alkyl halides allowed the synthesis of various new o- and p-alkylselenenylated benzoic acid derivatives in good yields. The anti-inflammatory activity of selected selenide derivatives on granuloma induced by subcutaneous implantation of cotton pellets in Wistar rats was examined. Selenium derivatives 2a, 2c and 2e showed anti-inflammatory activity although to a lesser extent as compared to indomethacin, however they were found less toxic than the latter.
Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Compostos de Selênio/síntese química , Compostos de Selênio/farmacologia , Animais , Anti-Inflamatórios/química , Feminino , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Ratos , Ratos Wistar , Compostos de Selênio/químicaRESUMO
Plant nonspecific lipid transfer proteins (nsLTPs) are characterized by their ability to bind a broad range of hydrophobic ligands in vitro. Their biological function has not yet been elucidated, but they could play a major role in plant defense to physical and biological stress. An nsLTP was isolated from Amaranthus hypochondriacus seeds and purified by gel filtration and reversed-phase high-performance liquid chromatography techniques. The molecular mass of the protein as determined by mass spectrometry is 9747.29 Da. Data from amino acid sequence, circular dichroism and binding/displacement of a fluorescent lipid revealed that it belongs to the nsLTP1 family. The protein shows the alpha-helical secondary structure typical for plant nsLTPs 1 and shares 40 to 57% sequence identity with nsLTPs 1 from other plant species and 100% identity with an nsLTP1 from Amaranthus caudatus. A model structure of the protein in complex with stearate based on known structures of maize and rice nsLTPs 1 suggests a protein fold complexed with lipids closely related to that of maize nsLTP1.
Assuntos
Amaranthus/química , Proteínas de Transporte/química , Modelos Moleculares , Análise de Sequência de Proteína , Amaranthus/classificação , Amaranthus/metabolismo , Sequência de Aminoácidos , Antígenos de Plantas , Proteínas de Transporte/classificação , Proteínas de Transporte/isolamento & purificação , Proteínas de Transporte/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Dicroísmo Circular , Lipídeos/química , Dados de Sequência Molecular , Peso Molecular , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Ligação Proteica , Estrutura Secundária de Proteína , Especificidade da Espécie , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
C27H37O4Cl is orthorhombic, P2(1)2(1)2(1). The unit-cell dimensions at 293 K are a = 7.1388(15), b = 12.9836(14), c = 26.665(10)A, V = 2471.5(10)A3, Dx = 1.239 g/cm3, and Z = 4. The R value is 0.070 for 1458 observed reflections. The A, B, C and D rings occur in distorted envelope, distorted half-chair, chair, and envelope and a half-chair conformations. The molecules in the crystal are packed at the normal van der Waals distances.