Title:In Vivo Antimalarial and In Vitro Antileishmanial Activity of 4- Aminoquinoline Derivatives Hybridized to Isoniazid or Sulfa or Hydrazine Groups
Volume: 14
Issue: 5
Author(s): Roberta R. Soares, Luciana M. R. Antinarelli, Isabela de O. Souza, Isabela de O. Souza, Fernanda V. Lopes, Kézia K. G. Scopel, Elaine S. Coimbra, Adilson D. da Silva and Clarice Abramo*
Affiliation:
- Departamento de Parasitologia, Microbiologia e Imunologia, I.C.B., Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, Minas Gerais 36036-900,Brazil
Keywords:
Malaria, leishmaniasis, chemotherapy, quinoline derivatives, 4-aminoquinoline, hydrazine.
Abstract: Background: Quinoline-containing compounds have displayed an impressive array of
pharmacological actions over the years, including antiprotozoal activities.
Methods: In this work we evaluate antimalarial and antileishmanial activities of some aminoquinoline
(AMQ) derivatives hybridized to sulfa or isoniazid or hydrazine groups.
Results and Conclusion: In murine model of infection occasioned by P. berghei, compounds AMQa,
AMQ-d and AMQ-e have shown promising antiplasmodial activity inhibiting the multiplication
of parasites in a manner similar to chloroquine in some cases. For leishmaniasis, the majority of the
compounds exhibited a strong in vitro activity against amastigotes of L. braziliensis (IC50 values below
10 μg/mL). Furthermore, AMQ-f, -g and -h (IC50 of 2.1, 1.4 and 1.8 μg/mL against amastigotes
of L. braziliensis, respectively) showed IC50 values very close to miltefosine (IC50 1.6 mg/mL), the
reference drug. None of the compounds showed cytotoxicity in vitro against uninfected human erythrocytes
(HC50 > 500.0 μg/mL). These results provide evidence that the AMQ compounds are promising
candidates as antimalarial and leishmanicidal drugs, which are extremely important considering
that these are endemic parasitic diseases in tropical countries and sometimes occur concurrently.
