Ketone- and Cyano-Selenoesters to Overcome Efflux Pump, Quorum-Sensing, and Biofilm-Mediated Resistance

The emergence of drug-resistant pathogens leads to a gradual decline in the efficacy of many antibacterial agents, which poses a serious problem for proper therapy. Multidrug resistance (MDR) mechanisms allow resistant bacteria to have limited uptake of drugs, modification of their target molecules, drug inactivation, or release of the drug into the extracellular space by efflux pumps (EPs). In previous studies, selenoesters have proved to be promising derivatives with a noteworthy antimicrobial activity. On the basis of these results, two series of novel selenoesters were synthesized to achieve more potent antibacterial activity on Gram-positive and Gram-negative bacteria. Fifteen selenoesters (eight ketone-selenoesters and seven cyano-selenoesters) were investigated with regards to their efflux pump-inhibiting, anti-quorum-sensing (QS), and anti-biofilm effects in vitro. According to the results of the antibacterial activity, the ketone-selenoesters proved to be more potent antibacterial compounds than the cyano-selenoesters. With regard to efflux pump inhibition, one cyano-selenoester on methicillin-resistant S. aureus and one ketone-selenoester on Salmonella Typhimurium were potent inhibitors. The biofilm inhibitory capacity and the ability of the derivatives to disrupt mature biofilms were noteworthy in all the experimental systems applied. Regarding QS inhibition, four ketone-selenoesters and three cyano-selenoesters exerted a noteworthy effect on Vibrio campbellii strains.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); Consejo Superior de Investigaciones Científicas (CSIC, Spain, project LINKA20285); and Czech Ministry of Education, Youth and Sports INTER-COST LTC19007, COST Action CA17104 STRATAGEM.Peer reviewe

The Anticancer and Chemopreventive Activity of Selenocyanate-Containing Compounds

Purpose of the Review: The aim of this work is to review systematically the selenocyanate-containing compounds reported so far with potential applications in cancer prevention and in cancer treatment, attempting to focus on the most active selenocyanate derivatives. Recent Findings: The chemopreventive and anticancer activity of selenocyanate-containing compounds as p-xylene selenocyanate and benzyl selenocyanate was found long time ago and has been deeply studied, revealing that this functional group can affect to very different cellular and metabolic targets. In the last years, novel active compounds that combine the selenocyanate moiety with different heterocycles, quinones, or steroids have been reported, renewing the interest in this selenium-containing functional group and discovering compounds with promising properties. Generally, these compounds show antiproliferative or cytotoxic activity, although certain ones are potent antioxidant agents. The novel heterocyclic compounds are mostly substituted with a –CHSeCN moiety but longer aliphatic linkers between the ring core and the –SeCN group can be also found. Isatins, quinazolines, oxadiazoles, pyrimidinones, and tacrines can be highlighted among the heterocycles found in novel active compounds, whereas certain derivatives of diosgenin and cholestane are active steroid-containing selenocyanates. Summary: Selenocyanates are a promising class of selenocompounds that generally show interesting properties as chemopreventive or as anticancer agents.Authors would like to thank the financial support of the Spanish BAgencia Estatal Consejo Superior de Investigaciones Científicas^ (CSIC, Spanish National Research Council), through the project 201780I027.Peer Reviewe