<abstract xmlns="http://www.w3.org/1999/xhtml"><p>Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic ineffectiveness occurs in 5 to 20 % of the cases. Therefore, it is essential to propose new pharmacological agents against this disease. In this work, esters of quinoxaline-7-carboxylate-1,4-di-<italic>N</italic>-oxide (EQX-<italic>N</italic>O) were evaluated in <italic>in vitro</italic> assays as novel trichomonicidal agents. Additionally, an <italic>in vitro</italic> enzyme assay and molecular docking analysis against triosephosphate isomerase of <italic>Trichomonas vaginalis</italic> to confirm their mechanism of action were performed. Ethyl (compound <bold>12</bold>) and <italic>n</italic>-propyl (compound <bold>37</bold>) esters of quinoxaline-7-carboxy-late-1,4-di-<italic>N</italic>-oxide derivatives showed trichomonicidal activity comparable to nitazoxanide, whereas five methyl (compounds <bold>5</bold>, <bold>15</bold>, <bold>19</bold>, <bold>20</bold> and <bold>22</bold>), four isopropyl (compounds <bold>28</bold>, <bold>29</bold>, <bold>30</bold> and <bold>34</bold>), three ethyl (compounds <bold>4</bold>, <bold>13</bold> and <bold>23</bold>) and one <italic>n</italic>propyl (compound <bold>35</bold>) ester derivatives displayed activity comparable to albendazole. Compounds <bold>6</bold> and <bold>20</bold> decreased 100 % of the enzyme activity of recombinant protein triosephosphate isomerase.</p></abstract>

Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic ineffectiveness occurs in 5 to 20 % of the cases. Therefore, it is essential to propose new pharmacological agents against this disease. In this work, esters of quinoxaline-7-carboxylate-1,4-di-N-oxide (EQX-NO) were evaluated in in vitro assays as novel trichomonicidal agents. Additionally, an in vitro enzyme assay and molecular docking analysis against triosephosphate isomerase of Trichomonas vaginalis to confirm their mechanism of action were performed. Ethyl (compound 12) and n-propyl (compound 37) esters of quinoxaline-7-carboxy-late-1,4-di-N-oxide derivatives showed trichomonicidal activity comparable to nitazoxanide, whereas five methyl (compounds 5, 15, 19, 20 and 22), four isopropyl (compounds 28, 29, 30 and 34), three ethyl (compounds 4, 13 and 23) and one npropyl (compound 35) ester derivatives displayed activity comparable to albendazole. Compounds 6 and 20 decreased 100 % of the enzyme activity of recombinant protein triosephosphate isomerase.

Esters of quinoxaline-7-carboxylate-1,4-di-<italic>N</italic>-oxide as <italic>Trichomonas vaginalis</italic> triosephosphate isomerase inhibitors

Instituto Mexicano del Seguro Social Col. Industrial

Neglected Diseases Section, Drug R & D Unit Center for Applied Pharmacobiology Research University of Navarra

Laboratorio de Biotecnología Farmacéutica

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Esters of quinoxaline-7-carboxylate-1,4-di--oxide as  triosephosphate isomerase inhibitors

Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic...

Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors

Data publikacji: 31 gru 2020

Zakres stron: 485 - 495

Przyjęty: 09 paź 2020

DOI: https://doi.org/10.2478/acph-2021-0032

Słowa kluczowe
quinoxaline 1, 4-di--oxide, trichomoniasis, triosephosphate isomerase inhibitor

© 2021 Isidro Palos et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors

Data publikacji: 31 gru 2020

Zakres stron: 485 - 495

Przyjęty: 09 paź 2020

DOI: https://doi.org/10.2478/acph-2021-0032

Słowa kluczowequinoxaline 1, 4-di--oxide, trichomoniasis, triosephosphate isomerase inhibitor

© 2021 Isidro Palos et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Słowa kluczowe
quinoxaline 1, 4-di--oxide, trichomoniasis, triosephosphate isomerase inhibitor