DNA topoisomerases play a pivotal role in the regulation of cell division. Inhibition of Leishmania spp. topoisomerases represents an alternative to control parasite growth. Cancer research led to the development of several potent topoisomerase inhibitors such as topoisomerase I, topoisomerase II, or both (monobenzimidazole, terbenzimidazole, and protoberberine alkaloid-related compounds) that are effective antitumor agents. In the present study, we evaluated the efficacy of these compounds against Leishmania spp. growth in vitro. Some protoberberine compounds showed pronounced antileishmanial activity and were selected for further analysis in macrophages. These compounds did not affect macrophage viability and only slightly reduced macrophage nitric oxide generation in response to interferon-γ. Moreover, exposure of infected macrophages to these compounds significantly reduced parasite loads. Collectively, our data suggest that protoberberine-related compounds have powerful antileishmania action and that minor structural variations among them can substantially improve their activity to restrict Leishmania spp. infection in vitro.
Skip Nav Destination
Article navigation
October 2003
THERAPEUTICS-DIAGNOSTICS|
October 01 2003
EFFECTS OF TOPOISOMERASES INHIBITORS PROTOBERBERINE ON LEISHMANIA DONOVANI GROWTH, MACROPHAGE FUNCTION, AND INFECTION
Jean-François Marquis;
Jean-François Marquis
Département de Biologie Médicale, Faculté de Médecine, Centre de Recherche en Infectiologie du CHUQ, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2. [email protected]
Search for other works by this author on:
Darshan Makhey;
Darshan Makhey
Département de Biologie Médicale, Faculté de Médecine, Centre de Recherche en Infectiologie du CHUQ, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2. [email protected]
* Cancer Institute of New Jersey, New Brunswick, NJ 08901
† Department of Pharmaceutical Chemistry, Busch Campus, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854
Search for other works by this author on:
Edmond J. LaVoie;
Edmond J. LaVoie
Département de Biologie Médicale, Faculté de Médecine, Centre de Recherche en Infectiologie du CHUQ, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2. [email protected]
* Cancer Institute of New Jersey, New Brunswick, NJ 08901
† Department of Pharmaceutical Chemistry, Busch Campus, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854
Search for other works by this author on:
Martin Olivier
Martin Olivier
Département de Biologie Médicale, Faculté de Médecine, Centre de Recherche en Infectiologie du CHUQ, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2. [email protected]
‡ Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada H3A 2B4
§ Centre de Recherche en Infectiologie du CHUQ, Département de Biologie Médicale, Faculté de Médecine, Université Laval, Sainte-Foy, Québec, Canada G1V 4G2
‖ To whom correspondence should be addressed
Search for other works by this author on:
J Parasitol (2003) 89 (5): 1048–1052.
Citation
Jean-François Marquis, Darshan Makhey, Edmond J. LaVoie, Martin Olivier; EFFECTS OF TOPOISOMERASES INHIBITORS PROTOBERBERINE ON LEISHMANIA DONOVANI GROWTH, MACROPHAGE FUNCTION, AND INFECTION. J Parasitol 1 October 2003; 89 (5): 1048–1052. doi: https://doi.org/10.1645/GE-3161
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionCiting articles via
MOLECULAR AND NEW MORPHOLOGICAL DATA ON NEMATODE HEDRURIS DRATINI FOUND PARASITIZING PSEUDIS MINUTA (ANURA: HYLIDAE)
Martin M. Montes, Yasmin Croci, Jorge Barneche, Dario Balcazar, German F. Reig Cardarella, Sergio R. Martorelli
CLITELLATE (ANNELIDA: CLITELLATA) PARASITES AND PREDATORS OF NORTH AMERICAN HERPETOFAUNA: CHECKLIST OF SPECIES, IDENTIFICATION KEY, AND A NEW RECORD FOR MEXICO
Manuel De Luna, Roberto García-Barrios, Diane P. Barton, Leonardo García-Vázquez
LOUSY ASSOCIATIONS: SUCKING LICE (PHTHIRAPTERA: ANOPLURA) PARASITIZING RODENTS AND LAGOMORPHS IN THE DESERT NATIONAL WILDLIFE REFUGE, NEVADA
Sara B. Weinstein, John P. Dumbacher, Lance A. Durden
A NEW SPECIES OF ACANTHOBOTHRIUM (CESTODA: ONCHOPROTEOCEPHALIDEA), PARASITE OF THE GIANT ELECTRIC RAY NARCINE ENTEMEDOR JORDAN AND STARKS, 1895 (BATOIDEA: TORPEDINIFORMES) FROM MEXICO
Erick Rodríguez-Ibarra, Berenice Adán-Torres, Fernando Ruiz-Escobar, Gerardo Torres-Carrera
SEROPREVALENCE OF TOXOPLASMA GONDII IN GOATS FROM SOUTHWESTERN MISSISSIPPI, USA
Alexander D. W. Acholonu, Jamela S. Alexander