| Literature DB >> 30743174 |
Abdul-Malek S Al-Tamimi1, Mikel Etxebeste-Mitxeltorena2, Carmen Sanmartín2, Antonio Jiménez-Ruiz3, Leo Syrjänen4, Seppo Parkkila5, Silvia Selleri6, Fabrizio Carta7, Andrea Angeli8, Claudiu T Supuran9.
Abstract
We report new organoselenium compounds bearing the sulfonamide moiety as effective inhibitors of the β-isoform of Carbonic Anhydrase from the unicellular parasitic protozoan L. donovani chagasi. All derivatives were evaluated in vitro for their leishmanicidal activities against Leishmania infantum amastigotes along with their cytotoxicities in human THP-1 cells. Compounds 3e-g showed their activity in the low micromolar range with IC50 values spanning from 0.72 to 0.81 µM and selectivity indexes (SI) > 8 (for 3g SI > 30), thus much higher than those observed for the reference drugs miltefosine and edelfosine. This is the first study which reports new selenoderivatives with promising leishmanicidal properties and acting as Carbonic Anhydrase inhibitors too thus paving the way to the development of innovative agents for the treatment of neglected diseases such as leishmaniasis.Entities:
Keywords: Carbonic anhydrase; Inhibitor; Leishmania; Metalloenzymes; Selenium
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Year: 2019 PMID: 30743174 DOI: 10.1016/j.bioorg.2019.01.069
Source DB: PubMed Journal: Bioorg Chem ISSN: 0045-2068 Impact factor: 5.275