Unveiling a New Selenocyanate as a Multitarget Candidate with Anticancer, Antileishmanial and Antibacterial Potential

Abstract

Currently, cancer, leishmaniasis and bacterial infections represent a serious public health burden worldwide. Six cinnamyl and benzodioxyl derivatives incorporating selenium (Se) as selenocyanate, diselenide, or selenide were designed and synthesized through a nucleophilic substitution and/or a reduction using hydrides. Ferrocene was also incorporated by a Friedel–Crafts acylation. All the compounds were screened in vitro for their antiproliferative, antileishmanial, and antibacterial properties. Their capacity to scavenge free radicals was also assessed as a first approach to test their antioxidant activity. Benzodioxyl derivatives 2a–b showed cytotoxicity against colon (HT-29) and lung (H1299) cancer cell lines, with IC50 values below 12 µM, and were also fairly selective when tested in nonmalignant cells. Selenocyanate compounds 1–2a displayed potent antileishmanial activity in L. major and L. infantum, with IC50 values below 5 µM. They also exhibited antibacterial activity in six bacterial strains, notably in S. epidermidis with MIC and MBC values of 12.5 µg/mL. Ferrocene-containing selenide 2c was also identified as a potent antileishmanial agent with radical scavenging activity. Remarkably, derivative 2a with a selenocyanate moiety was found to act as a multitarget compound with antiproliferative, leishmanicidal, and antibacterial activities. Thus, the current work showed that 2a could be an appealing scaffold to design potential therapeutic drugs for multiple pathologies.

First Generation of Antioxidant Precursors for Bioisosteric Se-NSAIDs: Design, Synthesis, and In Vitro and In Vivo Anticancer Evaluation

“…Nevertheless, the Se-NSAID derivatives displayed an increase in their antioxidant activity over time, this effect is clearly observed at the highest concentration tested (Figure 3B). Thus, compounds 1-4 showed values of around 20-30% by the end of the experiment, surpassing the radical scavenging activity of other reported selenocompounds with therapeutic properties [22,66,78]. Remarkably, compound 5 was found to display the most potent radical scavenging activity among all the Se-NSAID derivatives, achieving values even comparable to those of the positive controls by the end of the assay (Figure 3B).…”

“…The antioxidant activity of the novel diacyl diselenide-based compounds was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetric assay following a previously published procedure [ 22 ]. Briefly, the compounds were dissolved at a concentration of 1 mg/mL in absolute methanol, and a dilution was prepared.…”

“…The efficacy of selenocompounds as anticancer agents is correlated with their metabolic route, dose, and the chemical form of Se [ 5 , 18 ]. Hence, the main Se entities that have been widely explored to date are selenides [ 19 , 20 , 21 , 22 ], selenocyanates [ 22 , 23 , 24 , 25 , 26 ], isoselenocyanates [ 27 , 28 , 29 ], selenazo heterocyclic compounds [ 13 , 30 , 31 ], selenoesters [ 32 , 33 , 34 ], selenoureas [ 35 , 36 , 37 , 38 , 39 ], and diselenides [ 19 , 22 , 23 , 24 , 25 , 39 , 40 ]. Additionally, several compounds bearing these functionalities have also been reported to have a potent radical scavenging capacity, allowing the design of molecules with an interesting dual profile as antioxidant and antiproliferative agents [ 19 , 25 , 37 , 38 ].…”

To Cut the Mustard: Antimicrobial Activity of Selenocyanates on the Plate and in the Gas Phase

“…Organic selenocyanates can also be synthesized by a variety of different routes, as described in the literature and presented in Figure 1, Panel a [1]. Selenocyanates have been reported to exhibit excellent anti-leishmanial, antichagasic, anticancer and antibacterial activities [8][9][10]. Moreover, members of this class of RSeS are able to modulate oxidative stress, attenuate catalase activity, and upregulate superoxide dismutase in cultured neuronal cells exposed to H 2 O 2 [11].…”