title: Selenocyanates and diselenides: a new class of potent antileishmanial agents.
abstract: Thirty five selenocyanate and diselenide compounds were subjected to in vitro screening against Leishmania infantum promastigotes and the most active ones were also tested in an axenic amastigote model. In order to establish the selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines. Thirteen derivatives exhibit better IC(50) values than miltefosine and edelfosine. Bis(4-aminophenyl)diselenide exhibits the best activity when assayed in infected macrophages and one of the lowest cytotoxic activities against the human cell lines tested, with SI values of 32 and 24 against Jurkat and THP-1 cells, respectively. This compound thus represents a new lead for further studies aimed at establishing its mechanism of action.
authors.affiliation: Sección de Síntesis, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Baquedano
authors.forename: David
authors.initials: D
authors.lastname: Moreno-Mateos
authors.forename: María
authors.initials: M
authors.lastname: Font
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Ruiz
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Palop
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
mesh_terms: D000627:Aminophenols / Q000737:chemistry; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003485:Cyanates / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology; D008018:Life Cycle Stages / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D018036:Selenium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000627:Aminophenols; D000981:Antiprotozoal Agents; D003485:Cyanates; D010742:Phospholipid Ethers; D018036:Selenium Compounds; D010767:Phosphorylcholine; C026659:edelfosine; C039128:miltefosine; C053721:selenocyanic acid