title: Synthesis, leishmanicidal and cytotoxic activity of triclosan-chalcone, triclosan-chromone and triclosan-coumarin hybrids.
abstract: Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7-9 and 17, were active against Leishmania parasites (EC50=9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25-27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.
authors.affiliation: Química de Plantas Colombianas, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, A.A 1226 Medellín, Colombia. elverluisotero@yahoo.es.
authors.forename: Elver
authors.initials: E
authors.lastname: Otero
authors.affiliation: Química de Plantas Colombianas, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, A.A 1226 Medellín, Colombia. sebitasnano@hotmail.com.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Vergara
authors.affiliation: PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 62 No. 52-59, Lab 632, A.A 1226 Medellín, Colombia. sara.robledo@udea.edu.co.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Robledo
authors.affiliation: Química de Plantas Colombianas, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, A.A 1226 Medellín, Colombia. wilson.cardona1@udea.edu.co.
authors.forename: Wilson
authors.initials: W
authors.lastname: Cardona
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain. mcarda@qio.uji.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 62 No. 52-59, Lab 632, A.A 1226 Medellín, Colombia. ivan.velez@udea.edu.co.
authors.forename: Ivan D
authors.initials: ID
authors.lastname: Vélez
authors.affiliation: SIN-BIO-ME-NA, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, A.A 1226 Medellín, Colombia. kimikrlos@hotmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rojas
authors.affiliation: SIN-BIO-ME-NA, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, A.A 1226 Medellín, Colombia. pipelion@quimica.udea.edu.co.
authors.forename: Felipe
authors.initials: F
authors.lastname: Otálvaro
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D014260:Triclosan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D047188:Chalcones; D003374:Coumarins; D014260:Triclosan