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.
Highlights
Leishmaniasis is a group of diseases caused by protozoan parasites of the genus Leishmania, which infect and replicate inside macrophages of the vertebrate host
Triclosan-chalcone hybrids 7–10 were obtained via microwave assisted Williamson etherification [35] between bromoalkyltriclosan 2–5 and 3,4-dimethoxy-4'-hydroxychalcone (6)
The crude reaction mixture was concentrated on a rotatory evaporator, and the residue was purified by column chromatography over silica gel eluting with hexane-ethyl acetate (9:1 ratio) to obtain the triclosan-chalcone hybrids in yields between 35%–60%
Summary
Leishmaniasis is a group of diseases caused by protozoan parasites of the genus Leishmania, which infect and replicate inside macrophages of the vertebrate host. The diseases is a major health problem because is present in 98 countries and three territories worldwide, affecting mostly low-income people in rural areas of tropical and subtropical countries. 0.7 to 1.2 million cutaneous leishmaniasis (CL) cases occur annually. Leishmania (Viannia) panamensis is one of the most important causal agent of CL in Central and. The different forms of leishmaniasis require expensive treatments, and the currently used medicines, pentavalent antimonials, pentamidine isothianate and miltefosine, show high toxicity and severe side effects and there is an urgent need for new drugs [3]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call