In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens
The work seeks to identify molecules with inhibitory activity against the DNA gyrase of Gram-negative microorganisms resistant to fluoroquinolones. Previously designed compounds were used to study antimicrobial potential in silico. Molecular docking was performed with nine new ciprofloxacin analog m...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Chemistry Proceedings |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-4583/8/1/43 |
| _version_ | 1797612764101869568 |
|---|---|
| author | Manuel Alejandro Coba-Males Javier Santamaría-Aguirre Christian D. Alcívar-León |
| author_facet | Manuel Alejandro Coba-Males Javier Santamaría-Aguirre Christian D. Alcívar-León |
| author_sort | Manuel Alejandro Coba-Males |
| collection | DOAJ |
| description | The work seeks to identify molecules with inhibitory activity against the DNA gyrase of Gram-negative microorganisms resistant to fluoroquinolones. Previously designed compounds were used to study antimicrobial potential in silico. Molecular docking was performed with nine new ciprofloxacin analog molecules, optimized through the PM6/ZDO theory level, in GyrA wild type (WT) and mutant type (MT) of <i>C. jejuni</i>, <i>E. coli</i> (6RKU PDB ID), <i>N. gonorrhoeae</i>, <i>P. aeruginosa</i>, <i>S. enteritidis</i>, and <i>S. typhi</i>. The molecule with the highest affinity for GyrA was selected based on its binding free energy and inhibition constant. In addition, a retrospective docking was carried out, to guarantee the correct affinity of the ligand to the receptor at the defined binding site. The results show a molecule with greater affinity for GyrA in five microorganisms, showing a binding free energy of less than −7.0 kcal/mol, suggesting a good antibacterial activity in silico. |
| first_indexed | 2024-03-11T06:46:36Z |
| format | Article |
| id | doaj.art-59b7148a302d47a49eb2acbee476c63b |
| institution | Directory Open Access Journal |
| issn | 2673-4583 |
| language | English |
| last_indexed | 2024-03-11T06:46:36Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Chemistry Proceedings |
| spelling | doaj.art-59b7148a302d47a49eb2acbee476c63b2023-11-17T10:18:37ZengMDPI AGChemistry Proceedings2673-45832021-11-01814310.3390/ecsoc-25-11753In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative PathogensManuel Alejandro Coba-Males0Javier Santamaría-Aguirre1Christian D. Alcívar-León2Facultad de Ciencias Químicas, Universidad Central del Ecuador, Quito 170521, EcuadorDNA Replication and Genome Instability Unit, Grupo de Investigación en Biodiversidad, Zoonosis y Salud Pública (GIBCIZ), Instituto de Investigación en Zoonosis-CIZ, Facultad de Ciencias Químicas, Universidad Central del Ecuador, Quito 170521, EcuadorFacultad de Ciencias Químicas, Universidad Central del Ecuador, Quito 170521, EcuadorThe work seeks to identify molecules with inhibitory activity against the DNA gyrase of Gram-negative microorganisms resistant to fluoroquinolones. Previously designed compounds were used to study antimicrobial potential in silico. Molecular docking was performed with nine new ciprofloxacin analog molecules, optimized through the PM6/ZDO theory level, in GyrA wild type (WT) and mutant type (MT) of <i>C. jejuni</i>, <i>E. coli</i> (6RKU PDB ID), <i>N. gonorrhoeae</i>, <i>P. aeruginosa</i>, <i>S. enteritidis</i>, and <i>S. typhi</i>. The molecule with the highest affinity for GyrA was selected based on its binding free energy and inhibition constant. In addition, a retrospective docking was carried out, to guarantee the correct affinity of the ligand to the receptor at the defined binding site. The results show a molecule with greater affinity for GyrA in five microorganisms, showing a binding free energy of less than −7.0 kcal/mol, suggesting a good antibacterial activity in silico.https://www.mdpi.com/2673-4583/8/1/43molecular dockingfluoroquinolonesDNA gyrasebacterial resistance |
| spellingShingle | Manuel Alejandro Coba-Males Javier Santamaría-Aguirre Christian D. Alcívar-León In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens Chemistry Proceedings molecular docking fluoroquinolones DNA gyrase bacterial resistance |
| title | In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens |
| title_full | In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens |
| title_fullStr | In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens |
| title_full_unstemmed | In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens |
| title_short | In Silico Evaluation of New Fluoroquinolones as Possible Inhibitors of Bacterial Gyrases in Resistant Gram-Negative Pathogens |
| title_sort | in silico evaluation of new fluoroquinolones as possible inhibitors of bacterial gyrases in resistant gram negative pathogens |
| topic | molecular docking fluoroquinolones DNA gyrase bacterial resistance |
| url | https://www.mdpi.com/2673-4583/8/1/43 |
| work_keys_str_mv | AT manuelalejandrocobamales insilicoevaluationofnewfluoroquinolonesaspossibleinhibitorsofbacterialgyrasesinresistantgramnegativepathogens AT javiersantamariaaguirre insilicoevaluationofnewfluoroquinolonesaspossibleinhibitorsofbacterialgyrasesinresistantgramnegativepathogens AT christiandalcivarleon insilicoevaluationofnewfluoroquinolonesaspossibleinhibitorsofbacterialgyrasesinresistantgramnegativepathogens |