Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors
<i>Helicobacter pylori</i> (<i>H. pylori</i>) is a pathogen that can remain in the stomach of an infected person for their entire life. As a result, this leads to the development of severe gastric diseases such as gastric cancer. In addition, current therapies have several pr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/16/4955 |
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| author | Beatriz Hernández-Ochoa Gabriel Navarrete-Vázquez Rodrigo Aguayo-Ortiz Paulina Ortiz-Ramírez Laura Morales-Luna Víctor Martínez-Rosas Abigail González-Valdez Fernando Gómez-Chávez Sergio Enríquez-Flores Carlos Wong-Baeza Isabel Baeza-Ramírez Verónica Pérez de la Cruz Saúl Gómez-Manzo |
| author_facet | Beatriz Hernández-Ochoa Gabriel Navarrete-Vázquez Rodrigo Aguayo-Ortiz Paulina Ortiz-Ramírez Laura Morales-Luna Víctor Martínez-Rosas Abigail González-Valdez Fernando Gómez-Chávez Sergio Enríquez-Flores Carlos Wong-Baeza Isabel Baeza-Ramírez Verónica Pérez de la Cruz Saúl Gómez-Manzo |
| author_sort | Beatriz Hernández-Ochoa |
| collection | DOAJ |
| description | <i>Helicobacter pylori</i> (<i>H. pylori</i>) is a pathogen that can remain in the stomach of an infected person for their entire life. As a result, this leads to the development of severe gastric diseases such as gastric cancer. In addition, current therapies have several problems including antibiotics resistance. Therefore, new practical options to eliminate this bacterium, and its induced affections, are required to avoid morbidity and mortality worldwide. One strategy in the search for new drugs is to detect compounds that inhibit a limiting step in a central metabolic pathway of the pathogen of interest. In this work, we tested 55 compounds to gain insights into their possible use as new inhibitory drugs of <i>H. pylori</i> glucose-6-phosphate dehydrogenase (HpG6PD) activity. The compounds <b>YGC-1</b>; <b>MGD-1, MGD-2; TDA-1</b>; and <b>JMM-3</b> with their respective scaffold 1,3-thiazolidine-2,4-dione; <i>1H</i>-benzimidazole; 1,3-benzoxazole, morpholine, and biphenylcarbonitrile showed the best inhibitory activity (IC<sub>50</sub> = 310, 465, 340, 204 and 304 μM, respectively). We then modeled the HpG6PD protein by homology modeling to conduct an in silico study of the chemical compounds and discovers its possible interactions with the HpG6PD enzyme. We found that compounds can be internalized at the NADP<sup>+</sup> catalytic binding site. Hence, they probably exert a competitive inhibitory effect with NADP<sup>+</sup> and a non-competitive or uncompetitive effect with G6P, that of the compounds binding far from the enzyme’s active site. Based on these findings, the tested compounds inhibiting HpG6PD represent promising novel drug candidates against <i>H. pylori</i>. |
| first_indexed | 2024-03-10T08:33:35Z |
| format | Article |
| id | doaj.art-c8ba929ac18b4022926390f3521aaec6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:33:35Z |
| publishDate | 2021-08-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c8ba929ac18b4022926390f3521aaec62023-11-22T08:54:25ZengMDPI AGMolecules1420-30492021-08-012616495510.3390/molecules26164955Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase InhibitorsBeatriz Hernández-Ochoa0Gabriel Navarrete-Vázquez1Rodrigo Aguayo-Ortiz2Paulina Ortiz-Ramírez3Laura Morales-Luna4Víctor Martínez-Rosas5Abigail González-Valdez6Fernando Gómez-Chávez7Sergio Enríquez-Flores8Carlos Wong-Baeza9Isabel Baeza-Ramírez10Verónica Pérez de la Cruz11Saúl Gómez-Manzo12Programa de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, Cuernavaca, Morelos 62209, MexicoDepartamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoLaboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, MexicoLaboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, MexicoPrograma de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoDepartamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, MexicoLaboratorio de Inmunología Experimental, Instituto Nacional de Pediatría, Ciudad de México 04530, MexicoLaboratorio de EIMyT, Grupo de Investigación en Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, MexicoLaboratorio de Biomembranas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoLaboratorio de Biomembranas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoNeurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Ciudad de México 14269, MexicoLaboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico<i>Helicobacter pylori</i> (<i>H. pylori</i>) is a pathogen that can remain in the stomach of an infected person for their entire life. As a result, this leads to the development of severe gastric diseases such as gastric cancer. In addition, current therapies have several problems including antibiotics resistance. Therefore, new practical options to eliminate this bacterium, and its induced affections, are required to avoid morbidity and mortality worldwide. One strategy in the search for new drugs is to detect compounds that inhibit a limiting step in a central metabolic pathway of the pathogen of interest. In this work, we tested 55 compounds to gain insights into their possible use as new inhibitory drugs of <i>H. pylori</i> glucose-6-phosphate dehydrogenase (HpG6PD) activity. The compounds <b>YGC-1</b>; <b>MGD-1, MGD-2; TDA-1</b>; and <b>JMM-3</b> with their respective scaffold 1,3-thiazolidine-2,4-dione; <i>1H</i>-benzimidazole; 1,3-benzoxazole, morpholine, and biphenylcarbonitrile showed the best inhibitory activity (IC<sub>50</sub> = 310, 465, 340, 204 and 304 μM, respectively). We then modeled the HpG6PD protein by homology modeling to conduct an in silico study of the chemical compounds and discovers its possible interactions with the HpG6PD enzyme. We found that compounds can be internalized at the NADP<sup>+</sup> catalytic binding site. Hence, they probably exert a competitive inhibitory effect with NADP<sup>+</sup> and a non-competitive or uncompetitive effect with G6P, that of the compounds binding far from the enzyme’s active site. Based on these findings, the tested compounds inhibiting HpG6PD represent promising novel drug candidates against <i>H. pylori</i>.https://www.mdpi.com/1420-3049/26/16/4955<i>Helicobacter pylori</i>glucose-6-phosphate dehydrogenaseinhibitorsdockinghomology modelingdrug candidates |
| spellingShingle | Beatriz Hernández-Ochoa Gabriel Navarrete-Vázquez Rodrigo Aguayo-Ortiz Paulina Ortiz-Ramírez Laura Morales-Luna Víctor Martínez-Rosas Abigail González-Valdez Fernando Gómez-Chávez Sergio Enríquez-Flores Carlos Wong-Baeza Isabel Baeza-Ramírez Verónica Pérez de la Cruz Saúl Gómez-Manzo Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors Molecules <i>Helicobacter pylori</i> glucose-6-phosphate dehydrogenase inhibitors docking homology modeling drug candidates |
| title | Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors |
| title_full | Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors |
| title_fullStr | Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors |
| title_full_unstemmed | Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors |
| title_short | Identification and In Silico Characterization of Novel <i>Helicobacter pylori</i> Glucose-6-Phosphate Dehydrogenase Inhibitors |
| title_sort | identification and in silico characterization of novel i helicobacter pylori i glucose 6 phosphate dehydrogenase inhibitors |
| topic | <i>Helicobacter pylori</i> glucose-6-phosphate dehydrogenase inhibitors docking homology modeling drug candidates |
| url | https://www.mdpi.com/1420-3049/26/16/4955 |
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