Metal Complexes Derived of Diosmin with Biological Activities in vitro

Maéli M F Civa,Ricardo L Tranquilin,Dayany Da S A Maciel,Susana N Diniz,Regina M S Pereira,Dirceu G De Souza,Renata G Silva,Márcio L Dos Santos,Cristina E Okuyama

doi:10.5539/jmsr.v9n1p10

Abstract

The coordination of metal ions with flavonoids is applied to improve its pharmacological properties. To evaluate the role of ions on diosmin new complexes with Fe(II), Cu(II) and Co(II) ions were synthetized and characterized by UV, FT-IR and XRD techniques and surface morphology by SEM. The biological activity of coordination complexes in vitro, the antioxidant (ABTS), antibacterial (disc diffusion and MIC) and antitumoral activities (MTT) were analyzed. Diosmin when reacting with Fe(II) at 50&ordm;C loses the sugar molecule becoming diosmetin (D) coordinated at 1D:1Fe ratio. In presence of Cu(II) and Co(II) at the same conditions besides losing the sugar, diosmin loses the methyl group at C4&rsquo; and H at C3&rsquo;, producing a new ligand and complexes at 1D:2Cu or Co ratio, to produce DCu and DCo, respectively. The coordination of Cu and Fe improve the antioxidant activity of diosmin. DCo was the only presented antibacterial activity. Additionally, a specific antitumor effect of diosmin and metal complexes upon human leukemia cells was demonstrated, suggesting an immune regulatory action. The anti-melanoma activity of DCo is 10 times better than diosmin. Metal coordination could be used to improve drug activity and to give direction to a new possibility of clinical use for diosmin.

Highlights

Diosmin is a glycoside flavone found in higher vascular citrus plants such as Meyer Lemons (Oesterle & Wander, 1925)
Others authors demonstrated diosmin zinc complex improved insulin sensitivity in a model of type 2 diabetes Mellitus induced in rats (Gopalakrishnan, Pillai, & Subramanian, 2015) To evaluate the role of ions on diosmin pharmacological properties, in the present study we described the synthesis of new complexes of diosmin with Fe(II), Cu(II) and Co(II) ions, followed by their characterization by FT-IR, UV, XRD, scanning electron micrographs (SEM), conductivity and elementary analysis
The diosmin complexes DCu, DCo and DFe were synthesized by a molar ratio of 1/4 of diosmin/metal salt

Summary

Introduction

Diosmin is a glycoside flavone found in higher vascular citrus plants such as Meyer Lemons (Oesterle & Wander, 1925). It is one of the polyphenolic complexes known as flavonoids. The basic structure of the flavonoids consists of two aromatic rings (noted A and B) linked through an oxygenated heterocyclic (C) ring. The heterocyclic ring condensed with the benzene ring, is either an alpha-pyrone (flavonols and flavones) or dihydroderivative (flavanols and flavanones) (Corcoran, McKay, & Blumberg, 2012). The position of the substituent in the aromatic rings of diosmin is in C-5, C-4’ and C-5’ and a double bond in the C2-C3 position, characterizing as a flavone (Middleton, 1984; Pietta, 2000)

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Conclusion