The Investigation of the Binding of 6-Mercaptopurine to Site I on Human Serum Albumin

Sochacka, Jolanta; Baran, W.

doi:10.1007/s10930-012-9449-y

Cited by 10 publications

(5 citation statements)

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“…As shown in Figure S4, two emission bands at 489 and 518 nm (which had been observed for the HSA/ 2a complex) were not observed. Moreover, the binding constant ( K b ) of the interaction of 6-HMP with HSA was found to be 1.213 × 10 3 M –1 at 310 K (Figure S5), which was in agreement with previous reports, and it was lower than the corresponding K b of 2a . The higher binding constant of 2a presented here confirms that coordination of [6-MP] − to the [Pt(ppy)] + moiety remarkably enhanced the activity of the whole complex and shows the impact of cycloplatinated coordination on the biochemistry of 6-HMP.…”

Section: Resultsmentioning

confidence: 99%

Cycloplatinated(II) Derivatives of Mercaptopurine Capable of Binding Interactions with HSA/DNA

et al. 2019

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In this study, two new bis-cyclometalated Pt(II) complexes, [Pt(C^N)-(S^N)] [S^N = deprotonated 6-mercaptopurine (6-MP) and C^N = deprotonated 2phenylpyridine (ppy), 2a; C^N = deprotonated benzo[h]quinoline (bhq), 2b], are synthesized by the reaction of [PtR(SMe 2 )(C^N)] (R = Me or p-MeC 6 H 4 ) with 1 equiv of 6-mercaptopurine (6-HMP) at room temperature. The complexes are fully characterized using 1 H and 13 C NMR spectroscopies, electrospray ionization mass spectrometry, and elemental analysis. Biomolecular interaction of complex 2a with human serum albumin (HSA) is studied by fluorescence, UV−vis, and circular dichroism (CD) spectroscopies. The binding constants (K b ) and number of binding sites (n) are evaluated using the Stern−Volmer equation. The intrinsic fluorescence of protein is quenched by a static quenching mechanism, with a binding constant of K b ∼ 10 5 reflecting a high affinity of complex 2a for HSA. The thermodynamic parameters (ΔH°, ΔG°, and ΔS°) indicate that the interaction is a spontaneous process and hydrophobic forces play a main role in the reaction. The displacement experiments demonstrate that the reactive binding sites of HSA to complex 2a are mainly located within its hydrophobic cavity in subdomain IIA (site I). Synchronous fluorescence spectra reveal that complex 2a affected the microenvironment of tryptophan-214 residues in subdomain IIA of HSA. In the case of interaction of complex 2b and HSA, because of overlapping of the emission spectra of complex 2b with HSA, chemometric approaches are applied. The results indicate significant interaction between the tryptophan residue of HSA and complex 2b. Moreover, the binding of Pt(II) complexes 2a and 2b causes a reduction of the α-helix content of HSA, as obtained by far-UV CD spectroscopy. The average binding distance (r) between Pt(II) complexes and HSA is obtained by Forster's resonance energytransfer theory. Also, a molecular docking simulation reveals that π−π-stacking and hydrophobic interactions between these complexes and HSA are significant. Furthermore, the interactions of platinum complexes, 2, with calf-thymus DNA (CT-DNA) are investigated. The UV−vis results and ethidium bromide competitive studies support an intercalative interaction of both Pt(II) complexes with DNA. The new complexes 2 are also screened for anticancer activities. The results show that complexes 2 exhibit significant anticancer activity against the K562 (chronic myelogenous leukemia) cell line.

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Section: Resultsmentioning

confidence: 99%

Cycloplatinated(II) Derivatives of Mercaptopurine Capable of Binding Interactions with HSA/DNA

et al. 2019

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“…The mechanism of drug-drug interaction can be competitive-both drugs bind to the same binding site, or independent-drugs bind to different binding sites and there is no interaction between them. Also, mutual interaction can emerge when the drugs bind to different binding sites, but the interaction of the displacer drug with HSA causes conformational changes and thus affects the target drug binding [9].…”

Section: Introductionmentioning

confidence: 99%

Applicability of capillary electrophoresis‐frontal analysis for displacement studies: Effect of several drugs on l‐tryptophan and lidocaine binding to human serum albumin

Nevídalová

Michalcová

Glatz

2020

J of Separation Science

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The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion, and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co-administration of drugs with the same binding site can affect the above-mentioned concentration and as a result the pharmacological behavior of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis-frontal analysis, and the obtained values of binding parameters were compared with the literature data. The effect of several drugs and site markers on the binding of l-tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high-throughput screening method for drug-protein binding studies.

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“…No entanto, toda a análise espectroscópica foi feita na forma enolato, pois vários das resultados experimentais são obtidos em pH básico pH fisiológico). 8,9 Na forma aniônica da fenilbutazona observa-se uma maior planaridade do anel de cinco membros (Fig. 2), contrariamente à forma protonada.…”

Section: Resultsunclassified

“…Já a nossa estratégia é puramente baseada na varredura relaxada ao longo de ângulos diedros preferenciais (discutida adiante), e (c) e nosso interesse está na análise espectroscópica da forma do enolato (forma aniônica da fenilbutazona), pois vários das resultados experimentais são obtidos em pH básico (pH fisiológico). 8,9 A presença de um plano de simetria na molécula de fenilbutazona, na forma cetônica confere à mesma a propriedade de girar o plano da luz plano polarizada. Assim, é possível utilizar informações de espectros de dicroísmo circular eletrônico (ECD) para caracterizar aspectos de sua estrutura molecular.…”

Section: Figura 1 Equilíbrio Ceto-enólico Da Fenilbutazonaunclassified

Study of relative stability of tautomeric forms of phenylbutazone and calculation of UV-Vis and ECD spectra

Souza¹,

Ximenes²,

Morgon³

2016

Revista Virtual De Química

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Abstract:In this work, a theoretical study was carried out to investigate the electronic structures of the deprotonated form of phenylbutazone. Considering a relaxed PES s a f o th ee sele ted dihed al a gles δ 1 , δ 2 , a d δ 3 ) and by the conformational analysis (Boltzmann distribution), at PM3 methodology, eight most important structures were obtained. These structures were optimized and the TD-DFT/PCM (aqueous solvent) at B3LYP/6-31G(d) level and calculations of the UV-Vis and ECD spectra were obtained at CAM-B3LYP/6-311++G(d,p) methodology. Absorption maxima occur at 230 to 250 nm.Keywords: TD-DFT; Electronic and Molecular Structures; Electronic Circular Dichroism;Phenylbutazone. ResumoNeste trabalho foi feito um estudo teórico das estruturas eletrônicas da forma desprotonada da fenilbutazona. Pela análise populacional de confôrmeros do ânion, o tidos a pa ti da va edu a SCAN elaxado de t ês gulos died os sele io ados δ 1 , δ 2 e δ 3 ) obteve-se um conjunto de 8 estruturas, no nível de cálculo PM3. Otimizou-se esses confôrmeros utilizando DFT (B3LYP/6-31G(d)) e nas geometrias de equilíbrio calculou-se os espectros eletrônicos UV-Vis e de dicroísmo circular eletrônico (ECD) empregando o método CAM-B3LYP/6-311++G(d,p), através do formalismo TD-DFT e com efeito de solvente aquoso descrito pelo método PCM. Os máximos de absorção observados ocorrem entre 230 a 250 nm.

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The Investigation of the Binding of 6-Mercaptopurine to Site I on Human Serum Albumin

Cited by 10 publications

References 50 publications

Cycloplatinated(II) Derivatives of Mercaptopurine Capable of Binding Interactions with HSA/DNA

Cycloplatinated(II) Derivatives of Mercaptopurine Capable of Binding Interactions with HSA/DNA

Applicability of capillary electrophoresis‐frontal analysis for displacement studies: Effect of several drugs on l‐tryptophan and lidocaine binding to human serum albumin

Study of relative stability of tautomeric forms of phenylbutazone and calculation of UV-Vis and ECD spectra

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