In this study, hybrids 7–12 and 19–24 were synthesized via Williamson reaction of O-Quinaldine alkyl bromide plus eugenol and O-triclosan alkyl bromide plus 8-hydroxyquinaldine, respectively. Structures of the products were elucidated by spectroscopic analysis. The compounds synthesized were evaluated for antileishmanial activity against L. panamensis amastigotes and cytotoxic activity against U-937 cells. The compounds 19, 20, and 21 that are 8-hydroxyquinaldine linked to triclosan by 3, 4, and 5-carbon space, respectively, were more active against axenic amastigotes (EC50 = 23.6, 9.7, and 4.1 lg/ml, respectively). Compounds 19 and 21 were also active against intracellular amastigotes with EC50 vales of 6.4 and 2.4 lg/ml, respectively, making these compounds promising for the development of new antileishmanial drugs.