Methyl divanillate: redox properties and binding affinity with albumin of an antioxidant and potential NADPH oxidase inhibitor

Autor(es)

de Vasconcelos, Debora Naliati ^[1] ; Lima, Angelica Nakagawa ^[2] ; Philot, Eric Allison ^[2] ; Scott, Ana Ligia ^[2] ; Ferreira Boza, Izabelle Amorim ^[1] ; de Souza, Aguinaldo Robinson ^[1] ; Morgon, Nelson Henrique ^[3] ; Ximenes, Valdecir Farias ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Sao Paulo State Univ, Fac Sci, Dept Chem, BR-17033360 Bauru, SP - Brazil

^[2] UFABC Fed Univ ABC, Lab Computat Biol & Bioinformat, BR-09210580 Santo Andre, SP - Brazil

^[3] Campinas State Univ UNICAMP, Inst Chem, Dept Phys Chem, BR-13083861 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: RSC ADVANCES; v. 9, n. 35, p. 19983-19992, JUL 1 2019.
• Citações Web of Science: 0

Resumo

Vanillic acid is a widely used food additive (flavouring agent, JECFA number: 959) with many reported beneficial biological effects. The same is true for its ester derivative (methyl vanillate, JECFA number: 159). Based on the increasing evidence that diapocynin, the dimer of apocynin (NADPH oxidase inhibitor), has some improved pharmacological properties compared to its monomer, here the dimer of methyl vanillate (MV), i.e., methyl divanillate (dimer of methyl vanillate, DMV) was synthesized and studied in the context of its redox properties and binding affinity with human serum albumin (HSA). We found that the antioxidant potency of DMV was significantly increased compared to MV. In this regard, the reduction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical by DMV was 30-fold more effective compared to MV. Ferric ion reduction was 4-fold higher and peroxyl radical reduction was 2.7-fold higher. The interaction with HSA was significantly improved (Stern-Vomer constants, 3.8 x 10(5) mol(-1) L and 2.3 x 10(4) mol(-1) L, for DMV and MV, respectively). The complexation between DMV and HSA was also evidenced by induced circular dichroism (ICD) signal generation in the former due to its fixation in the asymmetric protein pocket. Density-functional calculations (TD-DFT) showed that the ICD spectrum was related to a DMV conformation bearing a dihedral angle of approximately -60 degrees. Similar dihedral angles were obtained in the lowest and most populated DMV cluster poses obtained by molecular docking simulations. The computational studies and experimental displacement studies revealed that DMV binds preferentially at site I. In conclusion, besides being a powerful antioxidant, DMV is also a strong ligand of HSA. This is the first study on the chemical and biophysical properties of DMV, a compound with potential beneficial biological effects. (AU)

• Processo FAPESP: 14/50926-0 - INCT 2014: biodiversidade e produtos naturais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• Processo FAPESP: 16/20549-5 - Desenvolvimento e aplicação de sondas fluorescentes e baseadas em dicroísmo circular para estudos de interação de ligantes com proteínas, caracterização de proteínas amiloides e determinação de atividade enzimática
• Beneficiário: Valdecir Farias Ximenes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/22014-1 - Desenvolvimento de Sondas Fluorescentes para Determinação de Sítios de Ligação em Albumina: Estudo da Relação entre Estrutura Molecular, Constante de Associação e Especificidade
• Beneficiário: Luiza de Carvalho Bertozo
• Modalidade de apoio: Bolsas no Brasil - Doutorado