Review Article

Novel amidines and analogues as promising agents against intracellular parasites: a systematic review

M. N. C. SOEIROa1 c1, K. WERBOVETZa2, D. W. BOYKINa3, W. D. WILSONa3, M. Z. WANGa4 and A. HEMPHILLa5

a1 Laboratόrio de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

a2 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA

a3 Department of Chemistry, Georgia State University, Atlanta, GA 30302, USA

a4 Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, USA

a5 Institute of Parasitology, Vetsuisse Faculty of Veterinary Medicine, University of Berne, Berne, Switzerland


Parasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates.

(Received November 29 2012)

(Revised January 22 2013)

(Revised February 22 2013)

(Accepted March 01 2013)

(Online publication April 08 2013)

Key words

  • intracellular parasites;
  • chemotherapy;
  • aromatic amidines;
  • arylimidamides


c1 Corresponding author: Laboratόrio de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. E-mail: