Cyano-and ketone-containing selenoesters as multi-target compounds against resistant cancers

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”

Expression of osmotin, an antifungal protein from Nicotiana tabacum in Escherichia coli

Plants have evolved a huge variety of proteins involved in the defense against pathogens and adaptation to stressful environments. Plant proteins whose expression is strongly induced in response to infection by pathogens belong to the group of pathogenesis-related (PR) proteins. The family of PR-5 proteins constitutes a group of cysteine-rich proteins including thaumatin, zeamatin and also osmotin. Osmotin is a cationic protein of 205 residues and molecular weight of 24 kDa. It was discovered and characterized in cells of Nicotiana tabacum var. Wisconsin 38. The plasmid harbouring cDNA of osmotin from Nicotiana tabacum was constructed for transformation of Escherichia coli. The osmotin gene was prepared in fusion with histidine tail to facilitate the isolation and purification from bacterial cells. Selection of transgenic colonies was based on antibiotic resistance. The hexahistidine-tagged osmotin was overexpressed in heterologous system by using pET expression vector and purified using immobilized metal affinity chromatography. The expression of osmotin was detected and antifungal activity was tested

Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.The study was supported by the projects SZTE ́AOK-KKA 2018/270- 62-2 of the University of Szeged, Faculty of Medicine and GINOP- 2.3.2–15-2016–00038 (Hungary), Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC, Spain, mobility project LINKA20285). This research was funded by the mobility project from the Czech Min- istry 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, assessed on 30 December 2021). The study was also supported by two associations from the province of Zamora, Spain: “Asociaci ́on Cultural Trevinca” and “Ini- ciativas Ropelanas”. B.R. was supported by the project EFOP-3.6.3- VEKOP-16–2017-00009 (Hungary). N.S. was supported by the New National Excellence Program (ÚNKP)