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Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines
Author(s) -
FonsecaBerzal Cristina,
IbáñezEscribano Alexandra,
Vela Nerea,
Cumella José,
NogalRuiz Juan José,
Escario José Antonio,
da Silva Patrícia Bernardino,
Batista Marcos Meuser,
Soeiro Maria de Nazaré C.,
SifontesRodríguez Sergio,
MenesesMarcel Alfredo,
GómezBarrio Alicia,
Arán Vicente J.
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800084
Subject(s) - benznidazole , trypanosoma cruzi , trichomonas vaginalis , trichomoniasis , microbiology and biotechnology , leishmania , leishmaniasis , chagas disease , metronidazole , chemistry , amastigote , protozoa , antiprotozoal , biology , stereochemistry , in vitro , biochemistry , antibiotics , virology , parasite hosting , medicine , immunology , pathology , world wide web , computer science
Three different series of new 5‐nitroindazole derivatives—1‐(ω‐aminoalkyl)‐2‐benzylindazolin‐3‐ones (series A ; ten compounds), 3‐(ω‐aminoalkoxy)‐2‐benzylindazoles (series B ; four compounds) and 3‐alkylamino‐2‐benzylindazoles (series C ; five compounds)—have been synthesized and evaluated against the protozoan parasites Trypanosoma cruzi , Leishmania amazonensis , and Trichomonas vaginalis : etiological agents of Chagas disease, cutaneous leishmaniasis, and trichomoniasis, respectively. Many indazoles of series A , B , and C were efficient against T. cruzi . Some compounds in series A , after successfully passing the preliminary screening for epimastigotes, exhibited activity values against amastigotes of several T. cruzi strains that were better than or similar to those shown by the reference drug benznidazole and displayed low nonspecific toxicity against mammalian cells. On the other hand, preliminary studies against promastigotes of L. amazonensis showed high leishmanicidal activity for some derivatives of series A and C . With regard to activity against T. vaginalis , some indazoles of series B and C were rather efficient against trophozoites of a metronidazole‐sensitive isolate and showed low nonspecific toxicities toward Vero cell cultures. Additionally, some of these compounds displayed similar activity against metronidazole‐sensitive and resistant isolates, showing the absence of cross‐resistance between these derivatives and the reference drug.