Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities

摘要

The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeicacid hybrids are described herein. The structure of the synthesized products was elucidated by a com-bination of spectrometric analyses. The synthesized compounds were evaluated against amastigotesforms ofL. (V) panamensis, which is the most prevalentLeishmaniaspecies in Colombia, and againstTrypanosoma cruzi,which is the pathogenic species to humans. Cytotoxicity was evaluated against hu-man U-937 macrophages. Eight compounds were active againstL. (V) panamensis(18e23, 26and30) andeight of them againstT. cruzi(19e22,24and28e30) with EC50values lower than 40mM. Compounds19e22,24and28e30showed higher activities than benznidazole (BNZ). Esters19and21were the mostactive compounds for bothL. (V) panamensisandT. cruziwith 3.82 and 11.65mM and 8.25 and 8.69mM,respectively. Compounds19e22,24and28e30showed higher activities than benznidazole (BNZ). Mostof the compounds showed antiprotozoal activity and with exception of18,26and28, the remainingcompounds were toxic for mammalian cells, yet they have potential to be considered as candidates foranti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length ofthe alkyl linker with compound19, bearing a four-carbon alkyl chain, the most performing hybrid. Ingeneral, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond inthe side chain is not decisive for cytotoxicity and anti-protozoal activity.