TY - JOUR
T1 - 2′-Hydroxychalcones as an alternative treatment for trichomoniasis in association with metronidazole
AU - das Neves, Raquel Nascimento
AU - Sena-Lopes, Ângela
AU - Alves, Mirna Samara Dié
AU - da Rocha Fonseca, Bárbara
AU - da Silva, Caroline Carapina
AU - Casaril, Angela Maria
AU - Savegnago, Lucielli
AU - de Pereira, Claudio Martin Pereira
AU - Ramos, Daniela Fernandes
AU - Borsuk, Sibele
N1 - Funding Information:
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.
Funding Information:
This study was financed in part by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (CAPES) - Finance Code 001.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - The treatment for trichomoniasis, based on 5′-nitroimidazol agents, has been presenting failures related to allergic reactions, side effects, and the emergence of resistant isolates. There are no alternative drugs approved for the treatment of these cases; thus, the search for new active molecules is necessary. In this scenario, chalcones have been extensively studied for their promising biological activities. Here, we presented the synthesis of three hydroxychalcones (3a, b, and c), in vitro and in silico analyses against Trichomonas vaginalis. The in vitro biological evaluation showed that hydroxychalcone 3c presented anti-T. vaginalis activity, with complete death in 12 h of incubation at minimum inhibitory concentration (MIC) of 100 μM. 3c showed a dose-dependent cytotoxicity against mammalian VERO cell line, but the association of 3c at 12.5 μM and metronidazole (MTZ) at 40 μM showed 95.31% activity against T. vaginalis trophozoites after 24 h of exposure and did not affect the VERO cell growth, appearing to be a good alternative. In silico analysis by molecular docking showed that 3c could inhibit the activity of TvMGL (methionine gamma-lyase), TvLDH (lactate dehydrogenase), and TvPNP (purine nucleoside phosphorylase) affecting the T. vaginalis survival and also suggesting a different mechanism of action from MTZ. Therefore, these results propose that hydroxychalcones are promising anti-T. vaginalis agents and must be considered for further investigations regarding trichomoniasis treatment.
AB - The treatment for trichomoniasis, based on 5′-nitroimidazol agents, has been presenting failures related to allergic reactions, side effects, and the emergence of resistant isolates. There are no alternative drugs approved for the treatment of these cases; thus, the search for new active molecules is necessary. In this scenario, chalcones have been extensively studied for their promising biological activities. Here, we presented the synthesis of three hydroxychalcones (3a, b, and c), in vitro and in silico analyses against Trichomonas vaginalis. The in vitro biological evaluation showed that hydroxychalcone 3c presented anti-T. vaginalis activity, with complete death in 12 h of incubation at minimum inhibitory concentration (MIC) of 100 μM. 3c showed a dose-dependent cytotoxicity against mammalian VERO cell line, but the association of 3c at 12.5 μM and metronidazole (MTZ) at 40 μM showed 95.31% activity against T. vaginalis trophozoites after 24 h of exposure and did not affect the VERO cell growth, appearing to be a good alternative. In silico analysis by molecular docking showed that 3c could inhibit the activity of TvMGL (methionine gamma-lyase), TvLDH (lactate dehydrogenase), and TvPNP (purine nucleoside phosphorylase) affecting the T. vaginalis survival and also suggesting a different mechanism of action from MTZ. Therefore, these results propose that hydroxychalcones are promising anti-T. vaginalis agents and must be considered for further investigations regarding trichomoniasis treatment.
KW - Chalcones
KW - Molecular docking
KW - Synthesis
KW - T. vaginalis
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U2 - 10.1007/s00436-019-06568-4
DO - 10.1007/s00436-019-06568-4
M3 - Article
C2 - 31853622
AN - SCOPUS:85076807257
SN - 0932-0113
VL - 119
SP - 725
EP - 736
JO - Parasitology Research
JF - Parasitology Research
IS - 2
ER -