TY - JOUR
T1 - Expanding the chemical space of aryloxy-naphthoquinones as potential anti-Chagasic agents
T2 - synthesis and trypanosomicidal activity
AU - Becerra, Nohemí A.
AU - Espinosa-Bustos, Christian
AU - Vázquez, Karina
AU - Rivera, Gildardo
AU - Paulino, Margot
AU - Cantero, Jorge
AU - Nogueda, Benjamín
AU - Chacón-Vargas, Fabiola
AU - Castillo-Velazquez, Uziel
AU - Rodríguez, Ana F.Elizondo
AU - Toledo, Sofía
AU - Moreno-Rodríguez, Adriana
AU - Aranda, Mario
AU - Salas, Cristian O.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/12
Y1 - 2021/12
N2 - In continuation our effort to research the chemical space of aryloxy-naphthoquinones as potential anti-Chagas agents, we synthesized nine derivatives and these compounds were evaluated in vitro against the epimastigote and trypomastigote forms of Mexican strains of Trypanosoma cruzi (T. cruzi). Most of these derivatives are highly active against epimastigote forms (IC50 < 1.0 µM) compared to the reference drug benznidazole (Bzn). Then these were evaluated on trypomastigotes, which is showing better potency results than Bzn for compounds 3b and 3g. In addition, the cytotoxicity of these compounds was determined on the murine macrophage cell line J774. 3b and 3i were the most selective compounds against NINOA trypomastigote and INC-5 epimastigote forms, respectively. Further these compounds also have good oral bioavailability according to theoretical predictions. Finally, we were able to determine optimal substitution patterns using pharmacophoric models. All these results are provided very useful structural information to continue our designing of naphthoquinone derivatives against T. cruzi. [Figure not available: see fulltext.]
AB - In continuation our effort to research the chemical space of aryloxy-naphthoquinones as potential anti-Chagas agents, we synthesized nine derivatives and these compounds were evaluated in vitro against the epimastigote and trypomastigote forms of Mexican strains of Trypanosoma cruzi (T. cruzi). Most of these derivatives are highly active against epimastigote forms (IC50 < 1.0 µM) compared to the reference drug benznidazole (Bzn). Then these were evaluated on trypomastigotes, which is showing better potency results than Bzn for compounds 3b and 3g. In addition, the cytotoxicity of these compounds was determined on the murine macrophage cell line J774. 3b and 3i were the most selective compounds against NINOA trypomastigote and INC-5 epimastigote forms, respectively. Further these compounds also have good oral bioavailability according to theoretical predictions. Finally, we were able to determine optimal substitution patterns using pharmacophoric models. All these results are provided very useful structural information to continue our designing of naphthoquinone derivatives against T. cruzi. [Figure not available: see fulltext.]
KW - ADME properties
KW - Aryloxy-naphthoquinones
KW - Epimastigote
KW - Pharmacophoric analysis
KW - Trypanosoma cruzi
KW - Trypomastigote
UR - http://www.scopus.com/inward/record.url?scp=85117695661&partnerID=8YFLogxK
U2 - 10.1007/s00044-021-02809-3
DO - 10.1007/s00044-021-02809-3
M3 - Artículo
AN - SCOPUS:85117695661
SN - 1054-2523
VL - 30
SP - 2256
EP - 2265
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 12
ER -