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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.

journal of the brazilian chemical society

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