Pharmaceutical and Safety Profile Evaluation of Novel Selenocompounds with Noteworthy Anticancer Activity
Małgorzata Anna Marć,
Enrique Domínguez-Álvarez,
Gniewomir Latacz,
Agata Doroz-Płonka,
Carmen Sanmartín,
Gabriella Spengler,
Jadwiga Handzlik
Affiliations
Małgorzata Anna Marć
Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
Enrique Domínguez-Álvarez
Instituto de Química Orgánica General (IQOG-CSIC), Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, 28006 Madrid, Spain
Gniewomir Latacz
Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
Agata Doroz-Płonka
Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
Carmen Sanmartín
Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain
Gabriella Spengler
Albert Szent-Györgyi Health Center, Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary
Jadwiga Handzlik
Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
Prior studies have reported the potent and selective cytotoxic, pro-apoptotic, and chemopreventive activities of a cyclic selenoanhydride and of a series of selenoesters. Some of these selenium derivatives demonstrated multidrug resistance (MDR)-reversing activity in different resistant cancer cell lines. Thus, the aim of this study was to evaluate the pharmaceutical and safety profiles of these selected selenocompounds using alternative methods in silico and in vitro. One of the main tasks of this work was to determine both the physicochemical properties and metabolic stability of these selenoesters. The obtained results proved that these tested selenocompounds could become potential candidates for novel and safe anticancer drugs with good ADMET parameters. The most favorable selenocompounds turned out to be the phthalic selenoanhydride (EDA-A6), two ketone-containing selenoesters with a 4-chlorophenyl moiety (EDA-71 and EDA-73), and a symmetrical selenodiester with a pyridine ring and two selenium atoms (EDA-119).
