Synthesis, characterization and biological evaluation of Rutin–zinc(II) flavonoid -metal complex

• Published in: Chemico-biological interactions 2015-09, Vol.239, p.184-191
• Main Authors: Ikeda, Norma Estefania Andrades, Novak, Estela Maria, Maria, Durvanei Augusto, Velosa, Adélia Segin, Pereira, Regina Mara Silva
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antitumor; Apoptosis - drug effects; Apoptosis - genetics; Cell Line - drug effects; Chemistry Techniques, Synthetic; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Female; Flavonoids; Gene Expression Regulation - drug effects; Humans; Magnetic Resonance Spectroscopy; Membrane Potential, Mitochondrial - drug effects; Metal complex; Mice, Inbred BALB C; Molecular Structure; Paclitaxel - administration & dosage; Paclitaxel - pharmacology; Rutin; Rutin - chemistry; Rutin - pharmacology; Toxicity Tests, Subchronic; Xenograft Model Antitumor Assays; Zinc - chemistry
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2015.06.011

[Display omitted] •Rutin–zinc(II), a new flavonoid–metal complex was synthesized.•Rutin–zinc(II) showed antioxidant, cytotoxic, and antitumor properties.•The complexation with Zn(II) improved the biological activity of the free rutin.•Rutin–zinc(II) has no cytotoxicity against normal cells or in vivo toxicity.•Rutin–zinc(II) presented synergistic activity with paclitaxel. Synthesis of compounds analogous to natural products from secondary metabolites, such as flavonoids, is a promising source of novel drugs. Rutin (quercetin-3-O-rutinoside) is a natural flavone, which has, in its chemical structure, different sites for coordination with transition metals and the complexation with these metals enhances its biological properties. Rutin–zinc(II), a flavonoid–metal complex, was synthesized and characterized by UV–VIS, FT-IR, elemental analysis and 1H NMR. The antioxidant and antitumor activities, as well as the cytotoxicity and in vivo toxicity of this complex were evaluated and compared with the free rutin. Rutin–zinc(II) has not shown any cytotoxicity against normal cells (fibroblasts and HUVECs) or toxicity in BALB/c mice, but has shown antioxidant activity in vitro and cytotoxicity against leukemia (KG1, K562 and Jurkat), multiple myeloma (RPMI8226) and melanoma (B16F10 and SK-Mel-28) cell lines in vitro. In Ehrlich ascites carcinoma model, Rutin–zinc(II) modulated the mitochondrial membrane potential and the expression of genes related to cell cycle progression, angiogenesis and apoptosis.