In Vivo Antimalarial and In Vitro Antileishmanial Activity of 4-Aminoquinoline Derivatives Hybridized to Isoniazid or Sulfa or Hydrazine Groups

作者：Soares Roberta R; Antinarelli Luciana M R; Souza Isabela de O; Lopes Fernanda V; Scopel Kezia K G; Coimbra Elaine S; da Silva Adilson D; Abramo Clarice^*

来源：Letters in Drug Design and Discovery, 2017, 14(5): 597-604.

DOI：10.2174/1570180813666160927113743

• Malaria
• leishmaniasis
• chemotherapy
• quinoline derivatives
• 4-aminoquinoline
• hydrazine

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 AMQ-a, 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 mu g/mL). Furthermore, AMQ-f, -g and -h (IC50 of 2.1, 1.4 and 1.8 mu g/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 mu g/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.

• 出版日期2017