Introduction: Leishmaniasis is a major public health problem faced by many countries, including Colombia. Its treatment has limitations such as the toxicity of the drugs used, the emergence of resistant strains, and prolonged and expensive treatments. Thus, there is an urgent need to find alternative solutions.Objective: To evaluate the leishmanicidal and cytotoxic activities of three 2-styrylquinolines type compounds: 2-[(E)-2-(2,3-diacetyloxyphenyl)ethenyl]quinolin-8-yl-acetate, E1; 2-[(E)-2-(4-acetyloxy-3-methoxyphenyl)ethenyl] quinoline, E2, and 2-[(E)-2-(2,3-diacetyloxyphenyl)ethenyl] quinoline, E3.Materials and methods: The 2-styrylquinolines were obtained by organic synthesis using Perkintype condensation reaction from 8-hydroxy quinaldine or quinaldine and aromatic aldehydes. The leishmanicidal activity was evaluated on intracellular amastigotes of Leishmania (Viannia) panamensis by flow cytometry. The results were expressed as lethal concentration 50 (LC50) for cytotoxicity and effective concentration 50 (EC50) for leishmanicidal activity, calculated by the Probit method.Results: E3 showed high activity against L. (V) panamensis with a calculated EC50 value of 1.4 μg/ml, and a selectivity index of 3.9; E1 and E2 showed higher EC50 values of 5.6 and 68.1 μg/ml, respectively. For cytotoxicity, LC50 values ranging from 5.4 to 68.1 μg/ml were calculated. E2 was moderately toxic, showing an LC50 very similar to that of amphotericin B, a substance used as cytotoxic control.Conclusion: The styrylquinoline E3 is a promising compound against L. (V) panamensis, as it was able to significantly inhibit amastigotes inside the cell, reducing infection despite its toxicity.