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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: RSC ADVANCES; v. 9, n. 35, p. 19983-19992, JUL 1 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 16/20549-5 - Development and application of fluorescent probes and probes based on circular dichroism for the interaction studies of ligands with protein, characterization of amyloid proteins and determination of enzymatic activity
• Grantee: Valdecir Farias Ximenes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/22014-1 - Development of Fluorescent Probes for the Determination of Binding Sites on Albumin: Studies of the Relationship of the Molecular Structure, Association Constant and Specificity
• Grantee: Luiza de Carvalho Bertozo
• Support Opportunities: Scholarships in Brazil - Doctorate