A Comprehensive Evaluation of a Coumarin Derivative and Its Corresponding Palladium Complex as Potential Therapeutic Agents in the Treatment of Gynecological Cancers: Synthesis, Characterization, and Cytotoxicity
Mirela Jevtić,
Marijana Stanojević Pirković,
Teodora Komazec,
Marija Mojić,
Sanja Mijatović,
Danijela Maksimović-Ivanić,
Dušan Dimić,
Zoran Marković,
Dušica Simijonović,
Dejan Milenković,
Edina Avdović
Affiliations
Mirela Jevtić
Department of Gynecology and Obstetrics General Hospital Uzice, Miloša Obrenovića 17, 31000 Užice, Serbia
Marijana Stanojević Pirković
Department of Medical Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia
Teodora Komazec
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia
Marija Mojić
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia
Sanja Mijatović
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia
Danijela Maksimović-Ivanić
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia
Dušan Dimić
Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia
Zoran Marković
Department of Natural Science and Mathematics, State University of Novi Pazar, Vuka Karadžića bb, 36300 Novi Pazar, Serbia
Dušica Simijonović
Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia
Dejan Milenković
Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia
Edina Avdović
Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia
Background: The aim of this research is the synthesis and characterization of coumarin-palladium complex and the investigation of the cytotoxicity of both the ligand and the complex. Methods: The palladium( II) complex (CC) was obtained in the reaction between (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl-acetate (CL) and potassium-tetrachloropalladate(II) and characterized using IR and NMR spectra, experimentally and theoretically. Cytotoxicity of CL and CC were determined for human cervical carcinoma HeLa, ovarian cancer A2780, hormone dependent breast cancer MCF7, and colorectal cancer HCT116 lines. The interaction of investigated compounds with HSA was followed by spectrofluorimetric method. The binding mechanism in the active pocket was assessed via molecular docking simulations. Results: A low mean absolute error between experimental and theoretical data proved that the optimized structure corresponded to the experimental one. Both compounds showed a satisfactory selectivity index towards neoplastic cells. The binding affinity of tested compounds to the HSA were confirmed. The molecular docking showed a much lower change in the Gibbs free energy of binding for CC compared to CL. Conclusions: The obtained results revealed that CL and CC exhibit significant effects on several cancer cell lines and good binding properties to HSA, while molecular docking discovered that CC has the most pronounced activity against alpha-fetoprotein.
