Preparation of Rotenone Derivatives and in Vitro Analysis of Their Antimalarial, Antileishmanial and Selective Cytotoxic Activities
Yulieth Upegui,
Juan F. Gil,
Wiston Quiñones,
Fernando Torres,
Gustavo Escobar,
Sara M. Robledo,
Fernando Echeverri
Affiliations
Yulieth Upegui
PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Juan F. Gil
Grupo Química Orgánica de Productos Naturales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Wiston Quiñones
Grupo Química Orgánica de Productos Naturales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Fernando Torres
Grupo Química Orgánica de Productos Naturales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Gustavo Escobar
Grupo Química Orgánica de Productos Naturales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Sara M. Robledo
PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Fernando Echeverri
Grupo Química Orgánica de Productos Naturales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 70 #52-21, Medellín 050010, Colombia
Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC50 of 19.0 µM against P. falciparum, and 127.2 µM against L. panamensis. Although chemical transformation does not improve its biological profile against P. falciparum, three of its derivatives showed a significant level of action within an adequate range of activity with EC50 values < 50.0 µM. This antiplasmodial activity was not due to red blood cell hemolysis, since LC50 was >>400 µM. On the other hand, all derivatives displayed a non-specific cytotoxicity on several cell lines and primary human cell cultures.
