Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids

We report herein the synthesis and biological activities (cytotoxicity, leishmanicidal and trypanocidal) of six quinoline-chalcone and five quinoline-chromone hybrids. The synthesized compounds were evaluated against amastigotes forms of Leishmania (V) panamensis , which is the most prevalent Leishmania species in Colombia and Trypanosoma cruzi , which is the major pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Compounds 8 – 12 , 20 , 23 and 24 showed activity against Leishmania (V) panamensis , while compounds 9 , 10 , 12 , 20 and 23 had activity against Trypanosoma cruzi with EC 50 values lower than 18 mg mL −1 . 20 was the most active compound for both Leishmania (V) panamensis and Trypanosoma cruzi with EC 50 of 6.11 ± 0.26 μg mL −1 (16.91 μM) and 4.09 ± 0.24 (11.32 μM), respectively. All hybrids compounds showed better activity than the anti-leishmanial drug meglumine antimoniate. Compounds 20 and 23 showed higher activity than benznidazole, the current anti-trypanosomal drug. Although these compounds showed toxicity for mammalian U-937 cells,they still have the potential to be considered as candidates to antileishmanial or trypanocydal drug development.