Journal of Materials Science Research; Vol. 9, No. 1; 2019 ISSN 1927-0585 E-ISSN 1927-0593 Published by Canadian Center of Science and Education 10 Metal Complexes Derived of Diosmin with Biological Activities in vitro Maéli M. F. Civa 1 , Dirceu G. de Souza 1 , Renata G. Silva 1 , Dayany da S. A. Maciel 2 , Ricardo L. Tranquilin 3 , Susana N. Diniza 1,2 , Cristina E. Okuyama 1 , Márcio L. dos Santos 1,2 & Regina M. S. Pereira 1,2 1 Programa de Pós-graduação em Farmácia - Universidade Anhanguera São Paulo (UNIAN), São Paulo, Brazil 2 Programa de Pós-graduação em Biotecnologia e Inovação em Saúde - Universidade Anhanguera São Paulo (UNIAN), São Paulo, Brazil 3 CDMF-LIEC, UFSCar, São Carlos, SP, Brazil Correspondence: Regina M S Pereira, Programa de Pós-graduação em Farmácia - Universidade Anhanguera São Paulo (UNIAN), Av. Raimundo Pereira de Magalhães, 3305, CEP: 05145-200 São, Paulo- SP, Brazil. Tel: 55-11-3512-8415. E-mail: reginapereira1@anhanguera.com Received: November 14, 2019 Accepted: November 28, 2019 Online Published: December 6, 2019 doi:10.5539/jmsr.v9n1p10 URL: https://doi.org/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 50ºC 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’ and H at C3’, 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. Keywords: Diosmin, Complex, Antitumor, Antibacterial 1. 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. Flavonoids occur as aglycones, glycosides and methylated derivatives, and have an important role in the growth and development of plants, protecting then from ultraviolet-B (UV-B) radiation, fungal infection and microbial attack (Skaltsa, Verykokidou, Harvala, Karabourniotis, & Maneta, 1994; Grayer & Harborne, 1994; Harborne & Williams, 2000). 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 then as a flavone (Middleton, 1984; Pietta, 2000). The flavone diosmin presents pharmacological properties including antioxidant, anti-diabetic and anti-inflammatory properties (Tanaka, Kohno, & Mori, 2001; Browning, Walle, & Walle, 2005; Tahir et al., 2013). The antimicrobial effect was also observed for diverse flavonoids against different strains of bacteria, such as H. pylori, S. aureus, C. botulinum, E. Coli, P. aeruginosa and others (Moon et al., 2013; Ansari et al., 2015). However, neither of these studies demonstrated an antimicrobial effect of diosmin. Its mutagenic property was demonstrated by studies that investigated the effect of diosmin on prostate cancer (Lewinska, Siwak, Rzeszutek, & Wnuk, 2015) and other tumor lines. It was demonstrated that diosmin, at lower concentrations, induces senescence, apoptosis and autophagy in breast cancer cell lines (Lewinska, Adamczyk-Grochala, Kwasniewicz, Deregowska, & Wnuk,