Antileishmanial and Antitrypanosomal Activity of Synthesized Hydrazones, Pyrazoles, Pyrazolo[1,5-a]-Pyrimidines and Pyrazolo[3,4-b]- Pyridine

Title:Antileishmanial and Antitrypanosomal Activity of Synthesized Hydrazones, Pyrazoles, Pyrazolo[1,5-a]-Pyrimidines and Pyrazolo[3,4-b]- Pyridine

Volume: 14 Issue: 3

Author(s): Katherine Figarella, Sabrina Marsiccobetre, Ivan Galindo-Castro, Neudo Urdaneta, Julio C. Herrera, Nieves Canudas and Elier Galarraga*

Affiliation:

• Departmento de Quimica, Edificio de Quimica y Procesos, Universidad Simon Bolivar, Apartado 89000, Caracas 1080A,Venezuela

Keywords: Antileishmanial, antitrypanosomal, hydrazones, pyrazolo[1, 5-a]-pyrimidines, pyrazolo[3, 4-b]-pyridines, 6- substituted-3-formylchromones.

Abstract: Background: Considering the fact that many nitrogenated aromatic derivatives such as pyrazoles, hydrazones, pyrazolo[1,5-a]-pyrimidines and pyrazolo [3,4-b]-pyridine have shown antiparasitic properties, the current study was carried out to analyze the in vitro antileishmanial and antitrypanosomal potential of some derivatives, synthesize from 6-substituted-3-formylcromone.

Method: The pyrazoles (4a-c), hydrazones (5a-c), pyrazolo[1,5-a]-pyrimidines (6a, 6b) and pyrazolo [3,4-b]-pyridine (7) were prepared by condensation reaction between 6-substituted 3-formylchromones (1a-c) with N-substituted hydrazines (2a-c) and aminopyrazole 3. The synthesized compounds were tested for their in vitro antiparasitic activity against promastigotes of Leishmania mexicana (Bel 21) and epimastigotes of Trypanosoma cruzi (DM28) using a modified MTT assay to determine the compounds IC50 on each parasite strain. The selectivity index (SI) of each compound was also determined by testing the compounds on fibroblasts.

Results: IC50 values of all compounds were between 6 – 89 µM for L. mexicana and 4 – 174 µM for T. cruzi. Hydrazones 5a and 5b exhibited the highest antiparasitic activity against both L. mexicana, with IC50 values of 6.3 µM and 15 µM respectively, and T. cruzi, with IC50 4.1 µM and 10 µM and were 2 to 5 times more active on these parasites than on fibroblasts.

Conclusion: These results suggest that compound 5a is a suitable candidate for further development of molecules with antileishmanial and antitrypanosomal activity.

Cite this article as:

Figarella Katherine, Marsiccobetre Sabrina, Galindo-Castro Ivan , Urdaneta Neudo , Herrera C. Julio , Canudas Nieves and Galarraga Elier*, Antileishmanial and Antitrypanosomal Activity of Synthesized Hydrazones, Pyrazoles, Pyrazolo[1,5-a]-Pyrimidines and Pyrazolo[3,4-b]- Pyridine, Current Bioactive Compounds 2018; 14 (3) . https://dx.doi.org/10.2174/1573407213666170405121810