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Antichagasic profile of a Series of Mannich Base‐Type Derivatives: Design, Synthesis, in vitro Evaluation, and Computational Studies Involving Iron Superoxide Dismutase
Author(s) -
Paucar Rocío,
MartínEscolano Rubén,
MorenoViguri Elsa,
Cirauqui Nuria,
Marín Clotilde,
SánchezMoreno Manuel,
PérezSilanes Silvia
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201901108
Subject(s) - mannich base , trypanosoma cruzi , benznidazole , amastigote , in vitro , chagas disease , combinatorial chemistry , chemistry , superoxide dismutase , biochemistry , stereochemistry , pharmacology , biology , organic chemistry , enzyme , immunology , leishmania , computer science , parasite hosting , world wide web
Chagas disease is a silent disease that continues to endanger millions of people and, due to its insufficient current chemotherapy, urgently requires the development of more effective drugs. With this objective, twenty‐six Mannich base derivatives were synthesized, and their in vitro activity was evaluated against Trypanosoma cruzi . Three out of the twenty‐six compounds showed interesting results, including IC 50 values<10 μM and a selectivity index >20 in amastigote forms of Arequipa and SN3 T. cruzi strains. In addition, these compounds showed similar infection rates in Vero cells compared to those of benznidazole at 50 μM. Finally, some studies were performed to investigate the possible mechanism of action; moreover, computational studies proposed a binding mode of these derivatives to Fe‐SOD. This new series of compounds has an encouraging antichagasic profile with a simplified structure and synthetic routes. Therefore, the most active compounds should be considered as leads for further optimization of the antichagasic activity.