Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids

Molecules

Elver Otero²  Sebastián Vergara²  Sara M. Robledo⁴  Wilson Cardona²  Miguel Carda³  Ivan D. Vélez⁴  Carlos Rojas¹ 

[1] SIN-BIO-ME-NA, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia UdeA, Calle 70 No. 52-21, A.A 1226 Medellín, Colombia; E-Mails:;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; E-Mails:;Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, E-12071 Castellón, Spain; E-Mail:;PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 62 No. 52-59, Lab 632, A.A 1226 Medellín, Colombia; E-Mails:

关键词: leishmaniasis;    antiprotozoal;    triclosan;    coumarin;    chromone;    chalcone;    hybrids;   

DOI  :  10.3390/molecules190913251

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.