4.6 Article

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

Journal

MOLECULES
Volume 27, Issue 21, Pages -

Publisher

MDPI
DOI: 10.3390/molecules27217477

Keywords

selenium; cytotoxicity; antileishmanial activity; antibacterial activity; antioxidant

Funding

  1. Plan de Investigacion de la Universidad de Navarra, PIUNA (2018-19)
  2. Institute of Tropical Health of University of Navarra (ISTUN)
  3. Caixa Foundation
  4. Ubesol, Spain

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In this study, a series of selenium-containing compounds were designed and synthesized, and their antiproliferative, antileishmanial, and antibacterial activities were evaluated in vitro. Some of these compounds showed promising therapeutic potential against multiple pathologies, making them attractive candidates for drug development.
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 mu M, 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 mu M. They also exhibited antibacterial activity in six bacterial strains, notably in S. epidermidis with MIC and MBC values of 12.5 mu g/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.

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