Potential Antileishmanial Activity of 4-N-Acylhydrazone Pyrazolo[3,4-d]pyridazin-7-ones: Synthesis, in vitro Biological Evaluations and Computational Studies

In this work a series of 28 novel pyrazolo[3,4-d]pyridazin-7-ones were synthesized and tested against Leishmania amazonensis (strain WHOM/BR/75/JOSEFA) in promastigote and axenic amastigote forms. Five compounds were active against both cellular forms with IC50 (inhibitory concentration growth of 50...

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Published in:Journal of the Brazilian Chemical Society 2018-12, Vol.29 (12), p.2657-2668
Main Authors: Jacomini, Andrey, da Silva, Michael, Poletto, Julia, Ribeiro, Gessica, Yokoyama, Jessica, Bidóia, Danielle, Paula, Fávero, Nakamura, Celso, Sarragiotto, Maria Helena, Rosa, Fernanda
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CHEMISTRY, MULTIDISCIPLINARY
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container_end_page 2668
container_issue 12
container_start_page 2657
container_title Journal of the Brazilian Chemical Society
container_volume 29
creator Jacomini, Andrey
da Silva, Michael
Poletto, Julia
Ribeiro, Gessica
Yokoyama, Jessica
Bidóia, Danielle
Paula, Fávero
Nakamura, Celso
Sarragiotto, Maria Helena
Rosa, Fernanda
description In this work a series of 28 novel pyrazolo[3,4-d]pyridazin-7-ones were synthesized and tested against Leishmania amazonensis (strain WHOM/BR/75/JOSEFA) in promastigote and axenic amastigote forms. Five compounds were active against both cellular forms with IC50 (inhibitory concentration growth of 50%) values of 20.2, 11.7, 16.2, 29.5 and 40.3 µM for promastigote and 17.4, 25.2, 3.84, 21.8 and 22.7 µM for axenic amastigote. All compounds were studied by the Lipinski rule, cytotoxicity both in silico and in vitro to fibroblast line (L929) and macrophages (J774A1), and the most active compound showed a selectivity index of 59.9.
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title Potential Antileishmanial Activity of 4-N-Acylhydrazone Pyrazolo[3,4-d]pyridazin-7-ones: Synthesis, in vitro Biological Evaluations and Computational Studies
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