Synthesis and Characterization of Novel Copper(II)-Sunitinib Complex: Molecular Docking, DFT Studies, Hirshfeld Analysis and Cytotoxicity Studies
Facundo Tarasi,
Priscila Ailín Lanza,
Valeria Ferretti,
Gustavo Alberto Echeverría,
Oscar Enrique Piro,
Maximiliano Cacicedo,
Stephan Gehring,
Ignacio Esteban León,
María Soledad Islas
Affiliations
Facundo Tarasi
Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Mar del Plata 7600, Argentina
Priscila Ailín Lanza
QUIAMM (Grupo de Investigación en Química Analítica y Modelado Molecular), Vinculado a INBIOTEC-CONICET (Instituto de Investigaciones en Biodiversidad y Biotecnología), Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Mar del Plata 7600, Argentina
Valeria Ferretti
CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata. Blvd. 120 N° 1465, La Plata 1900, Argentina
Gustavo Alberto Echeverría
Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata e IFLP (CONICET, CCT-La Plata), C.C. 67, La Plata 1900, Argentina
Oscar Enrique Piro
Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata e IFLP (CONICET, CCT-La Plata), C.C. 67, La Plata 1900, Argentina
Maximiliano Cacicedo
Laboratory of Pediatric Immunology and Infectious Diseases, Children’s Hospital, University Medical Center, Johannes Gutenberg Mainz University, 55131 Mainz, Germany
Stephan Gehring
Laboratory of Pediatric Immunology and Infectious Diseases, Children’s Hospital, University Medical Center, Johannes Gutenberg Mainz University, 55131 Mainz, Germany
Ignacio Esteban León
CEQUINOR (UNLP, CCT-CONICET La Plata, Asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata. Blvd. 120 N° 1465, La Plata 1900, Argentina
María Soledad Islas
Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Mar del Plata 7600, Argentina
The main goal of this work was to report the synthesis, characterization, and cytotoxicity study of a novel copper(II)-sunitinib complex, CuSun. It has been synthesized and characterized in solid state and in solution by different methods (such as DFT, FTIR, Raman, UV-vis, EPR, NMR, etc.). The solid-state molecular structure of trichlorosunitinibcopper(II), where sunitinib: N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, for short Cu(Sun)Cl3, was determined by X-ray diffraction. It crystallizes in the triclinic space group P-1 with a = 7.9061(5) Å, b = 12.412(1) Å, c = 13.7005(8) Å, α = 105.021(6)°, β = 106.744(5)°, γ = 91.749(5)°, and Z = 2 molecules per unit cell. Also, we have found π-π interactions and classic and non-classic H-bonds in the crystal structure by using Hirshfeld surface analysis. In the speciation studies, the complex has dissociated in protonated sunitinib and chlorocomplex of copper(II), according to 1HNMR, EPR, UV-vis and conductimetric analysis. Molecular docking of the complex in both, ATP binding site and allosteric site of VEGFR2 have shown no improvement in comparison to the free ligand. Besides, cytotoxicity assay on HepG2 cell line shows similar activity for complex and ligand in the range between 1–25 μM supporting the data obtained from studies in solution.
