TY - JOUR
T1 - In vitro and in silico evaluations of new aryloxy-1,4-naphthoquinones as anti-Trypanosoma cruzi agents
AU - González, Alejandra
AU - Becerra, Nohemí
AU - Kashif, Muhammad
AU - González, Mercedes
AU - Cerecetto, Hugo
AU - Aguilera, Elena
AU - Nogueda-Torres, Benjamín
AU - Chacón-Vargas, Karla F.
AU - José Zarate-Ramos, J.
AU - Castillo-Velázquez, Uziel
AU - Salas, Cristian O.
AU - Rivera, Gildardo
AU - Vázquez, Karina
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - In the search for new therapeutic alternatives for Chagas disease, a series of six aryloxy -naphthoquinone derivatives were synthesized and evaluated in vitro against Trypanosoma cruzi epimastigotes of the Tulahuén 2, INC-5, and NINOA strains. The compounds 3d and 4a showed better or similar trypanosomicidal activity than the reference drug nifurtimox. In addition, 3d and 4a also elicited better trypanosomicidal activity than nifurtimox against T. cruzi bloodstream trypomastigotes. On the other hand, 3b showed the highest selective indexes (SI values between 44 and 500, in the three T. cruzi strains). Finally, molecular docking studies suggested that these compounds could be potential trypanothione reductase inhibitors. Therefore, based on these new results, we validated that the aryloxy-naphthoquinone scaffold is essential to obtain more selective cytotoxic and trypanosomicidal compounds.
AB - In the search for new therapeutic alternatives for Chagas disease, a series of six aryloxy -naphthoquinone derivatives were synthesized and evaluated in vitro against Trypanosoma cruzi epimastigotes of the Tulahuén 2, INC-5, and NINOA strains. The compounds 3d and 4a showed better or similar trypanosomicidal activity than the reference drug nifurtimox. In addition, 3d and 4a also elicited better trypanosomicidal activity than nifurtimox against T. cruzi bloodstream trypomastigotes. On the other hand, 3b showed the highest selective indexes (SI values between 44 and 500, in the three T. cruzi strains). Finally, molecular docking studies suggested that these compounds could be potential trypanothione reductase inhibitors. Therefore, based on these new results, we validated that the aryloxy-naphthoquinone scaffold is essential to obtain more selective cytotoxic and trypanosomicidal compounds.
KW - Aryloxy-naphthoquinones
KW - Chagas disease
KW - Cytotoxicity
KW - Molecular docking
KW - Trypanosoma cruzi
KW - Trypanothione reductase
UR - http://www.scopus.com/inward/record.url?scp=85078469246&partnerID=8YFLogxK
U2 - 10.1007/s00044-020-02512-9
DO - 10.1007/s00044-020-02512-9
M3 - Artículo
SN - 1054-2523
VL - 29
SP - 665
EP - 674
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 4
ER -