Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors
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,...
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2021-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0032 |
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| author | Palos Isidro Moo-Puc Rosa Vique-Sánchez José Luis Benítez-Cardoza Claudia G. Monge Antonio Villalobos-Rocha Juan Carlos Paz-Gonzalez Alma D. Rivera Gildardo |
| author_facet | Palos Isidro Moo-Puc Rosa Vique-Sánchez José Luis Benítez-Cardoza Claudia G. Monge Antonio Villalobos-Rocha Juan Carlos Paz-Gonzalez Alma D. Rivera Gildardo |
| author_sort | Palos Isidro |
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| description | 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. |
| format | Article |
| id | doaj-art-00666647180847f48fc02849e4c2a1c3 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-00666647180847f48fc02849e4c2a1c32025-02-02T12:35:53ZengSciendoActa Pharmaceutica1846-95582021-09-0171348549510.2478/acph-2021-0032acph-2021-0032Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitorsPalos Isidro0Moo-Puc Rosa1Vique-Sánchez José Luis2Benítez-Cardoza Claudia G.3Monge Antonio4Villalobos-Rocha Juan Carlos5Paz-Gonzalez Alma D.6Rivera Gildardo7Unidad Académica Multidisciplinaria, Reynosa-Rodhe, Universidad Autónoma de Tamaulipas, 88779 Reynosa, MéxicoUnidad de Investigación Médica Yucatán, Unidad Médica de Alta Especialidad, Centro Médico Ignacio García Téllez, Instituto Mexicano del Seguro Social Col. Industrial, 97150 Mérida, MéxicoLaboratorio de Investigación Bioquímica Escuela Nacional de Medicina y Homeopatía Instituto Politécnico Nacional, Guillermo Massieu Helguera No. 239, La Escalera Ticoman 07320 Ciudad de México, MéxicoLaboratorio de Investigación Bioquímica Escuela Nacional de Medicina y Homeopatía Instituto Politécnico Nacional, Guillermo Massieu Helguera No. 239, La Escalera Ticoman 07320 Ciudad de México, MéxicoNeglected Diseases Section, Drug R & D Unit Center for Applied Pharmacobiology Research University of Navarra, C/Irunlarrea, 31008Pamplona, SpainLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710 Reynosa, MéxicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710 Reynosa, MéxicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, 88710 Reynosa, MéxicoTrichomoniasis 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.https://doi.org/10.2478/acph-2021-0032quinoxaline 14-di-n-oxidetrichomoniasistriosephosphate isomerase inhibitor |
| spellingShingle | Palos Isidro Moo-Puc Rosa Vique-Sánchez José Luis Benítez-Cardoza Claudia G. Monge Antonio Villalobos-Rocha Juan Carlos Paz-Gonzalez Alma D. Rivera Gildardo Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors Acta Pharmaceutica quinoxaline 1 4-di-n-oxide trichomoniasis triosephosphate isomerase inhibitor |
| title | Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors |
| title_full | Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors |
| title_fullStr | Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors |
| title_full_unstemmed | Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors |
| title_short | Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors |
| title_sort | esters of quinoxaline 7 carboxylate 1 4 di n oxide as trichomonas vaginalis triosephosphate isomerase inhibitors |
| topic | quinoxaline 1 4-di-n-oxide trichomoniasis triosephosphate isomerase inhibitor |
| url | https://doi.org/10.2478/acph-2021-0032 |
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