Full Structural Characterization of Homoleptic Complexes of Diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo
Por:
Meza-Morales, William, Mirian Estevez-Carmona, M., Alvarez-Ricardo, Yair, Obregon-Mendoza, Marco A., Cassani, Julia, Teresa Ramirez-Apan, Maria, Escobedo-Martinez, Carolina, Soriano-Garcia, Manuel, Reynolds, William F., Enriquez, Raul G.
Publicada:
2 abr 2019
Resumen:
At the present time, scientists place a great deal of effort worldwide
trying to improve the therapeutic potential of metal complexes of
curcumin and curcuminoids. Herein, the synthesis of four homoleptic
metal complexes with diacetylcurcumin (DAC), using a ligand designed to
prevent the interaction of phenolic groups, rendering metal complexes
through the -diketone functionality, is reported. Due to their
physiological relevance, we used bivalent magnesium, zinc, copper, and
manganese for complexation with DAC. The resulting products were
characterized by ultraviolet-visible (UV-Vis), fluorescence
spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear
magnetic resonance (NMR), electron paramagnetic resonance (EPR),
magnetic moment, mass spectrometry (MS), single crystal, and powder
X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in
dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic
systems with space group P-1, showing the metal bound to the -diketone
function, while the H-1-NMR confirmed the preference of the enolic form
of the ligand. Single crystal data demonstrated a 1:2 metal:ligand
ratio. The inhibition of lipid peroxidation was evaluated using the
thiobarbituric acid reactive substance assay (TBARS). All four metal
complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 =
2.03 +/- 0.27, 1.58 +/- 0.07, 1.58 +/- 0.15 and 1.24 +/- 0.10 M
respectively) compared with butylated hydroxytoluene (BHT) and
-tocopherol. The cytotoxic activity in human cancer cell lines against
colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung
adenocarcinoma (SKLU-1) was found comparable ((DAC)(2)Mg), or ca. 2-fold
higher ((DAC)(2)Zn) than cisplatin. The acute toxicity assays indicate
class 5 toxicity, according to the Organization for Economic
Co-operation and Development (OECD) guidelines at doses of 3 g/kg for
all complexes. No mortality or changes in the behavior of animals in any
of the treated groups was observed. A therapeutic potential can be
envisaged from the relevant cytotoxic activity upon human cancer cell
lines in vitro and the undetected in vivo acute toxicity of these
compounds.
Filiaciones:
Meza-Morales, William:
Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City 07340, DF, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad UniversitariaCDMX CP 07340, Mexico
Mirian Estevez-Carmona, M.:
Inst Politecn Nacl, Escuela Nacl Ciencias Biol, Wilfrido Massieu SN, Mexico City 07738, DF, Mexico
Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Wilfrido Massieu SN, CDMX CP 07738, Mexico
Alvarez-Ricardo, Yair:
Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City 07340, DF, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad UniversitariaCDMX CP 07340, Mexico
Obregon-Mendoza, Marco A.:
Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City 07340, DF, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad UniversitariaCDMX CP 07340, Mexico
Cassani, Julia:
Univ Autonoma Metropolitana, Dept Sistemas Biol, Unidad Xochimilco, Mexico City 04960, DF, Mexico
Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad XochimilcoCDMX CP 04960, Mexico
Teresa Ramirez-Apan, Maria:
Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City 07340, DF, Mexico
Escobedo-Martinez, Carolina:
Univ Guanajuato, Dept Farm, Div Ciencias Nat & Exactas, Campus Guanajuato, Guanajuato 36050, Mexico
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Campus Guanajuato, Guanajuato CP, 36050, Mexico
Soriano-Garcia, Manuel:
Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City 07340, DF, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad UniversitariaCDMX CP 07340, Mexico
Reynolds, William F.:
Univ Toronto, Dept Chem, Toronto, ON M5S 1A1, Canada
Department of Chemistry, University of Toronto, Toronto, ON M5S 1A1, Canada
Enriquez, Raul G.:
Univ Nacl Autonoma Mexico, Inst Quim, Ciudad Univ, Mexico City 07340, DF, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad UniversitariaCDMX CP 07340, Mexico
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