Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents
<b>Background/Objectives:</b> Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-<i>Tryp...
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| author | Timoteo Delgado-Maldonado Diana V. Navarrete-Carriola Lenci K. Vázquez-Jiménez Alma D. Paz-González Baojie Wan Scott Franzblau Othman Mueen Mohammed Lorena Rodríguez-Páez Charmina Aguirre-Alvarado Verónica Alcántara-Farfán Joaquín Cordero-Martínez Debasish Bandyopadhyay Adriana Moreno-Rodríguez Gildardo Rivera |
| author_facet | Timoteo Delgado-Maldonado Diana V. Navarrete-Carriola Lenci K. Vázquez-Jiménez Alma D. Paz-González Baojie Wan Scott Franzblau Othman Mueen Mohammed Lorena Rodríguez-Páez Charmina Aguirre-Alvarado Verónica Alcántara-Farfán Joaquín Cordero-Martínez Debasish Bandyopadhyay Adriana Moreno-Rodríguez Gildardo Rivera |
| author_sort | Timoteo Delgado-Maldonado |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-<i>Trypanosoma cruzi</i>, anti-<i>Leishmania mexicana</i>, and anti-<i>Mycobacterium tuberculosis</i> agents. <b>Methods:</b> The compounds were synthesized by condensing 4-hydroxybenzhydrazide with appropriate aldehydes in acidic conditions and structurally confirmed by spectroscopic techniques. All compounds were evaluated in vitro against <i>T. cruzi</i> strains (NINOA and A1), <i>L. mexicana</i> (M379 and FCQEPS strains), and <i>M. tuberculosis</i> (H37Rv strain), followed by enzymatic assays against <i>T. cruzi</i> cysteine proteases. <b>Results:</b> Compound <b>Nfz-24</b> (IC<sub>50</sub> = 6.8 μM) had better trypanocidal activity than the reference drugs benznidazole (IC<sub>50</sub> > 30 μM) and nifurtimox (IC<sub>50</sub> > 7 μM) against the NINOA strain, and <b>Nfz-8</b> (IC<sub>50</sub> = 7.2 μM) was the compound most active against the A1 strain with a high inhibition of <i>T. cruzi</i> cysteine proteases (IC<sub>50</sub> = 4.6 μM) and low cytotoxic effects (CC<sub>50</sub> >100 μM). On the other hand, compound <b>Nfz-5</b> (IC<sub>50</sub> = 5.2 μM) had a 25-fold better leishmanicidal effect than glucantime (IC<sub>50</sub> > 125 μM) against the <i>L. mexicana</i> M379 strain, and compound <b>Nfz-13</b> had the best leishmanicidal effects (IC<sub>50</sub> = 10.2 μM) against the FCQEPS strain. Finally, <b>Nfz</b>, <b>Nfz-1</b>, and <b>Nfz-2</b> had minimum inhibitory concentration (MIC) values of 12.3, 5.1, and 18.8 μg/mL against <i>M. tuberculosis</i>, respectively. <b>Conclusions:</b> In summary, these results suggest that the compounds <b>Nfz-1</b>, <b>Nfz-2</b>, <b>Nfz-5</b>, <b>Nfz-8</b>, <b>Nfz-10</b>, <b>Nfz-15</b>, <b>Nfz-24</b>, and <b>Nfz-25</b> are candidates for further studies to develop new and more potent anti-<i>T. cruzi</i>, anti-leishmaniasis, and anti-<i>M. tuberculosis</i> agents. |
| format | Article |
| id | doaj-art-9e008834f9f24e8ea1b0d6b608eed20b |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-9e008834f9f24e8ea1b0d6b608eed20b2025-08-20T02:33:58ZengMDPI AGPharmaceutics1999-49232025-05-0117562110.3390/pharmaceutics17050621Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> AgentsTimoteo Delgado-Maldonado0Diana V. Navarrete-Carriola1Lenci K. Vázquez-Jiménez2Alma D. Paz-González3Baojie Wan4Scott Franzblau5Othman Mueen Mohammed6Lorena Rodríguez-Páez7Charmina Aguirre-Alvarado8Verónica Alcántara-Farfán9Joaquín Cordero-Martínez10Debasish Bandyopadhyay11Adriana Moreno-Rodríguez12Gildardo Rivera13Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, MexicoInstitute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, USAInstitute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, USADepartment of Medical Laboratories Techniques, College of Health and Medical Technology, University of Al Maarif, Al Anbar 31001, IraqDepartamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoDepartamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoDepartamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoDepartamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoSchool of Integrative Biological and Chemical Sciences (SIBCS), University of Texas Rio Grande Valley, Edinburg, TX 78539, USALaboratorio de Estudios Epidemiológicos, Clínicos, Diseños Experimentales e Investigación, Facultad de Ciencias Químicas, Universidad Autónoma “Benito Juárez” de Oaxaca, Avenida Universidad S/N, Oaxaca 68120, MexicoLaboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, Mexico<b>Background/Objectives:</b> Nifuroxazide (Nfz) is a drug that has been used as a scaffold for designing antimicrobial and antiparasitic agents. This study aimed to synthesize and evaluate in vitro of Nfz and twenty-five 4-hydroxybenzhydrazone derivatives as potential anti-<i>Trypanosoma cruzi</i>, anti-<i>Leishmania mexicana</i>, and anti-<i>Mycobacterium tuberculosis</i> agents. <b>Methods:</b> The compounds were synthesized by condensing 4-hydroxybenzhydrazide with appropriate aldehydes in acidic conditions and structurally confirmed by spectroscopic techniques. All compounds were evaluated in vitro against <i>T. cruzi</i> strains (NINOA and A1), <i>L. mexicana</i> (M379 and FCQEPS strains), and <i>M. tuberculosis</i> (H37Rv strain), followed by enzymatic assays against <i>T. cruzi</i> cysteine proteases. <b>Results:</b> Compound <b>Nfz-24</b> (IC<sub>50</sub> = 6.8 μM) had better trypanocidal activity than the reference drugs benznidazole (IC<sub>50</sub> > 30 μM) and nifurtimox (IC<sub>50</sub> > 7 μM) against the NINOA strain, and <b>Nfz-8</b> (IC<sub>50</sub> = 7.2 μM) was the compound most active against the A1 strain with a high inhibition of <i>T. cruzi</i> cysteine proteases (IC<sub>50</sub> = 4.6 μM) and low cytotoxic effects (CC<sub>50</sub> >100 μM). On the other hand, compound <b>Nfz-5</b> (IC<sub>50</sub> = 5.2 μM) had a 25-fold better leishmanicidal effect than glucantime (IC<sub>50</sub> > 125 μM) against the <i>L. mexicana</i> M379 strain, and compound <b>Nfz-13</b> had the best leishmanicidal effects (IC<sub>50</sub> = 10.2 μM) against the FCQEPS strain. Finally, <b>Nfz</b>, <b>Nfz-1</b>, and <b>Nfz-2</b> had minimum inhibitory concentration (MIC) values of 12.3, 5.1, and 18.8 μg/mL against <i>M. tuberculosis</i>, respectively. <b>Conclusions:</b> In summary, these results suggest that the compounds <b>Nfz-1</b>, <b>Nfz-2</b>, <b>Nfz-5</b>, <b>Nfz-8</b>, <b>Nfz-10</b>, <b>Nfz-15</b>, <b>Nfz-24</b>, and <b>Nfz-25</b> are candidates for further studies to develop new and more potent anti-<i>T. cruzi</i>, anti-leishmaniasis, and anti-<i>M. tuberculosis</i> agents.https://www.mdpi.com/1999-4923/17/5/621hydrazone moietynifuroxazidecysteine protease inhibitors<i>Leishmania mexicana</i><i>Trypanosoma cruzi</i>anti-<i>Mycobacterium tuberculosis</i> |
| spellingShingle | Timoteo Delgado-Maldonado Diana V. Navarrete-Carriola Lenci K. Vázquez-Jiménez Alma D. Paz-González Baojie Wan Scott Franzblau Othman Mueen Mohammed Lorena Rodríguez-Páez Charmina Aguirre-Alvarado Verónica Alcántara-Farfán Joaquín Cordero-Martínez Debasish Bandyopadhyay Adriana Moreno-Rodríguez Gildardo Rivera Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents Pharmaceutics hydrazone moiety nifuroxazide cysteine protease inhibitors <i>Leishmania mexicana</i> <i>Trypanosoma cruzi</i> anti-<i>Mycobacterium tuberculosis</i> |
| title | Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents |
| title_full | Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents |
| title_fullStr | Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents |
| title_full_unstemmed | Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents |
| title_short | Nifuroxazide and 4-Hydroxybenzhydrazone Derivatives as New Antiparasitic (<i>Trypanosoma cruzi</i> and <i>Leishmania mexicana</i>) and Anti-<i>Mycobacterium tuberculosis</i> Agents |
| title_sort | nifuroxazide and 4 hydroxybenzhydrazone derivatives as new antiparasitic i trypanosoma cruzi i and i leishmania mexicana i and anti i mycobacterium tuberculosis i agents |
| topic | hydrazone moiety nifuroxazide cysteine protease inhibitors <i>Leishmania mexicana</i> <i>Trypanosoma cruzi</i> anti-<i>Mycobacterium tuberculosis</i> |
| url | https://www.mdpi.com/1999-4923/17/5/621 |
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