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1.
An Acad Bras Cienc ; 93(4): e20200443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495202

RESUMO

Phytochemical studies of Cespedesia spathulata (Ochnaceae) leaves using 1H, 13C NMR, and GC-MS have led to the isolation of some metabolites identified for the first time in these species such as cathechin, epicatechin, vitexin, orientin, 6''-O-acetyl-vitexin, sitosterol, stigmasterol, phytol, 4,5-dihydrovomifoliol and a mixture of aliphatic methyl esters, together with ochnaflavone, which was previously isolated from this plant. The modulating activity of some fractions and compounds from Cespedesia spathulata towards tyrosinase enzyme was assayed by spectroscopic and theoretical means/experiments. The dichloromethane fraction (133 µg mL-1) and ochnaflavone (333 µM) inhibited tyrosinase activity by 20 % and 2.0 %, respectively, whereas the ethyl acetate fraction (666 µg mL-1) and ±catechins (catechin and epicatechin - 800 µM) activated it by 104 % and 384 %, respectively. Quantum chemical calculations suggested that catechin and epicatechin are better activators than L-DOPA by interacting with Cu (II) ions. Molecular docking results suggested that hydrogen bonding and hydrophobic interactions are the main binding forces between each tyrosinase activator and the amino acid residues inside the active protein binding pocket.


Assuntos
Ochnaceae , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta
2.
Carbohydr Res ; 501: 108274, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33657497

RESUMO

Monosaccharides, e.g. fructose, glucose, and arabinose are present in most foods consumed daily, whether, in natural or industrialized forms, and their concentration in the human bloodstream can impact the formation of advanced glycation end-products (AGEs, prevalent in people with diabetes) impacting the profile of Human Serum Albumin (HSA) in biodistribution of endogenous and exogenous compounds. Multiple spectroscopic techniques (UV-vis, circular dichroism, steady-state, and time-resolved fluorescence) combined with molecular docking showed that carbohydrates interact weakly and spontaneously via a ground-state association with HSA. The binding is enthalpically and entropically driven in the subdomain IIA (site I) and perturb weakly the secondary structure of the albumin. Hydrogen bonding and van der Waals forces are the main intermolecular interactions involved in the ligand binding, as well as hydrophobic effects related to the release of hydration shell upon ligand binding. Overall, the results indicated that an increase in glucose, fructose or arabinose level in the human bloodstream may cause functional perturbation on the binding capacity of albumin. Therefore, there is the necessity of carbohydrate level control in the bloodstream to not compromise the interaction and distribution of exogenous and endogenous compounds by HSA.


Assuntos
Monossacarídeos/química , Albumina Sérica Humana/química , Sítios de Ligação , Configuração de Carboidratos , Humanos , Termodinâmica
3.
J Photochem Photobiol B ; 211: 111991, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32798854

RESUMO

The present work reports the spectroscopic and theoretical evaluation of the interaction between calf-thymus DNA (CT-DNA) and free-base meso-tetra-(ruthenated) porphyrin (H2RuTPyP) or its corresponding Zn(II) complex (ZnRuTPyP). Spectroscopic measurements (UV-vis, circular dichroism and steady-state fluorescence emission) combined with theoretical molecular docking calculations suggest that Ru(II)-porphyrins interact with the DNA backbone by external mode via electrostatic forces. In addition, gel electrophoresis analysis demonstrate that these porphyrins promote efficient plasmidial DNA photocleavage upon white-light irradiation conditions, indicating H2RuTPyP and ZnRuTPyP as potential candidates for photodynamic therapy.


Assuntos
Complexos de Coordenação/química , Clivagem do DNA/efeitos da radiação , DNA/efeitos da radiação , Fármacos Fotossensibilizantes/química , Porfirinas/química , Rutênio/química , Zinco/química , Cátions/química , Complexos de Coordenação/farmacologia , Sequestradores de Radicais Livres/química , Luz , Simulação de Acoplamento Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/química , Eletricidade Estática , Relação Estrutura-Atividade
4.
Dalton Trans ; 49(45): 16278-16295, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32400785

RESUMO

New isomeric tetra-cationic porphyrins containing peripheral [Pd(bpy)Cl]+ units attached to pyridyl substituents were synthesized and fully characterized. The porphyrins present an intense Soret band located in the blue spectral region and an additional four weaker red-shifted Q bands in the visible spectral region (about 500-700 nm). The obtained Strickler-Berg parameters indicate fully spin and symmetry allowed transitions for all the observed absorption bands. Both porphyrins present two fluorescence emission bands, an intense one located around 650 nm and an additional weak red-shifted emission at ∼710 nm. Fluorescence decay time profiles were obtained showing bi-exponential decay. The interaction of the porphyrins with bovine serum albumin (BSA) was studied in detail by a fluorescence quenching method and molecular docking analysis. In addition, the photodynamical activity of the porphyrins in the photooxidation of BSA was determined and compared with the light-induced formation of reactive oxygen species (ROS) by electron paramagnetic resonance (EPR) allied with the spin trapping method. The results show that the Pd(ii)-bypyridyl tetra-cationic porphyrins are promising candidates for the photooxidation of biological substrates used in photodynamic therapy (PDT).

5.
Bioorg Med Chem Lett ; 27(15): 3546-3550, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28583798

RESUMO

In the search for compounds which may inhibit the development of melanomas, a series of thiosemicarbazones has been investigated as possible inhibitors of the tyrosinase enzyme. The results showed that all the thiosemicarbazones tested exhibited significant inhibitory effects on the enzyme. Thiosemicarbazones Thio-1, Thio-2, Thio-3 and Thio-4 substituted with oxygenate moieties, were better inhibitors (IC50 0.42, 0.35, 0.36 and 0.44mM, respectively) than Thio-5, Thio-6, Thio-7 and Thio-8. For the better inhibitors, molecular docking results suggested that the oxygen present in the para position of the aromatic ring is essential for the tyrosinase inhibition, due its high ability for complexation with Cu2+ ions. Inside the active protein pocket, Thio-2 - the best studied inhibitor - is able to interact with the amino acid residues His-155, Gly-170 and Val-172 via hydrogen bonding and hydrophobic force. Thio-2, containing a substituent on the aromatic ring similar to the substrate l-DOPA, showed a competitive inhibition mechanism as viewed in a Lineweaver-Burk plot. The same results were observed in the UV-Vis curves.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Agaricales/efeitos dos fármacos , Agaricales/enzimologia , Humanos , Levodopa/metabolismo , Melaninas/metabolismo , Melanoma/tratamento farmacológico , Melanoma/enzimologia , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/metabolismo
6.
Photochem Photobiol Sci ; 15(12): 1524-1535, 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27841431

RESUMO

MnTPPS is a metallic water soluble porphyrin with high potential to be used as a contrast agent in photoacoustic tomography. In order to fully understand the interaction between MnTPPS and serum albumin and to investigate the effect of the light induced fast in situ heat deposition by MnTPPS in the protein, we performed several experimental studies using fluorescence and circular dichroism spectroscopies, as well as photoacoustic calorimetry. To identify the possible binding site(s) of the metalloporphyrin in serum albumin and to help interpret the spectroscopic results, a molecular docking exercise was also carried out. The fluorescence data indicate a 1 : 1 stoichiometry for the complex BSA : MnTPPS. The molecular docking results suggest one binding site at the subdomain IB of albumin, where Trp-134 is found, as the main binding site for MnTPPS. The CD data indicate no significant conformational changes of the BSA secondary structure upon MnTPPS binding and even after several minutes of laser excitation of MnTPPS. TR-PAC results show that the in situ heat deposition from MnTPPS does not cause any significant transient conformational change to the BSA structure. In conclusion, this work demonstrates that MnTPPS, in addition to the necessary physical and chemical properties to be used as a contrast agent in photoacoustic tomography, can be effectively carried by albumin and that in situ heat release following light absorption does not cause any significant damage to the protein structure.


Assuntos
Temperatura Alta , Soroalbumina Bovina/química , Sítios de Ligação , Dicroísmo Circular , Simulação de Acoplamento Molecular , Porfirinas/química , Ligação Proteica
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 169: 175-81, 2016 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-27376757

RESUMO

Serum albumins present reversible pH dependent conformational transitions. A sudden laser induced pH-jump is a methodology that can provide new insights on localized protein (un)folding processes that occur within the nanosecond to microsecond time scale. To generate the fast pH jump needed to fast-trigger a protein conformational event, a photo-triggered acid generator as o-nitrobenzaldehyde (o-NBA) can be conveniently used. In order to detect potential specific or nonspecific interactions between o-NBA and BSA, we have performed ligand-binding studies using fluorescence spectroscopy, saturation transfer difference (STD) NMR, molecular docking and semi-empirical calculations. Fluorescence quenching indicates the formation of a non-fluorescent complex in the ground-state between the fluorophore and the quencher, but o-NBA does not bind much effectively to the protein (Ka~4.34×10(3)M(-1)) and thus can be considered a relatively weak binder. The corresponding thermodynamic parameters: ΔG°, ΔS° and ΔH° showed that the binding process is spontaneous and entropy driven. Results of (1)H STD-NMR confirm that the photo-acid and BSA interact, and the relative intensities of the signals in the STD spectra show that all o-NBA protons are equally involved in the binding process, which should correspond to a nonspecific interaction. Molecular docking and semi-empirical calculations suggest that the o-NBA binds preferentially to the Trp-212-containing site of BSA (FA7), interacting via hydrogen bonds with Arg-217 and Tyr-149 residues.


Assuntos
Benzaldeídos/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Benzaldeídos/química , Sítios de Ligação , Bovinos , Entropia , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Soroalbumina Bovina/química , Espectrometria de Fluorescência
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