Cyano- and Ketone-Containing Selenoesters as Multi-Target Compounds against Resistant Cancers
| Autor: | Noemi Salardón-Jiménez, Annamária Kincses, Márta Nové, Francisco-Javier Alonso-Martínez, Gabriella Spengler, Simona Dobiasová, Clotilde Sevilla-Hernández, Miguel Benito-Lama, Enrique Domínguez-Álvarez, Giyaullah Habibullah, Jitka Viktorova, Nikoletta Szemerédi |
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| Přispěvatelé: | University of Szeged, Consejo Superior de Investigaciones Científicas (España), Ministry of Education, Youth and Sports (Czech Republic), European Commission |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
03.03. Egészségtudományok Ketone Apoptosis Multidrug resistance Article Selenium multidrug resistance medicine Potency cancer Doxorubicin Cytotoxicity selenium RC254-282 Cancer chemistry.chemical_classification Efflux pump apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens 01.06. Biológiai tudományok ABCB1 Oncology chemistry Biochemistry Cancer cell efflux pump Efflux Wound healing medicine.drug |
| Zdroj: | Cancers, Vol 13, Iss 4563, p 4563 (2021) Cancers Volume 13 Issue 18 Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2072-6694 2016-0003 |
| Popis: | Fifteen selenocompounds, comprising of eight ketone-containing selenoesters (K1–K8, also known as oxoselenoesters) and seven cyano-containing selenoesters (N1–N7, known also as cyanoselenoesters), have been designed, synthesized, and evaluated as novel anticancer agents. These compounds are derivatives of previously reported active selenoesters and were prepared following a three-step one-pot synthetic route. The following evaluations were performed in their biological assessment: cytotoxicity determination, selectivity towards cancer cells in respect to non-cancer cells, checkerboard combination assay, ABCB1 inhibition and inhibition of ABCB1 ATPase activity, apoptosis induction, and wound healing assay. As key results, all the compounds showed cytotoxicity against cancer cells at low micromolar concentrations, with cyanoselenoesters being strongly selective. All of the oxoselenoesters, except K4, were potent ABCB1 inhibitors, and two of them, namely K5 and K6, enhanced the activity of doxorubicin in a synergistic manner. The majority of these ketone derivatives modulated the ATPase activity, showed wound healing activity, and induced apoptosis, with K3 being the most potent, with a potency close to that of the reference compound. To summarize, these novel derivatives have promising multi-target activity, and are worthy to be studied more in-depth in future works to gain a greater understanding of their potential applications against cancer. The study was supported by the projects SZTE ÁOK-KKA 2018/270-62-2 of the University of Szeged, Faculty of Medicine and GINOP-2.3.2-15-2016-00038 (Hungary); and Consejo Superior de Investigaciones Científicas (CSIC, Spain, project LINKA20285). This research was funded by VISEGRAD FUND, grant number 22010090; and by the mobility project from the Czech Ministry of Education, Youth and Sports INTER-COST, grant number LTC19007. This article is based upon work from COST Action 17104 , supported by COST (European Cooperation in Science and Technology), (http://www.cost.eu, accessed on 17 September 2021). The study was supported also by two cultural associations: “Trevinca” and “Iniciativas Ropelanas”. |
| Databáze: | OpenAIRE |
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