Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing
Tuberculosis (TB) remains a serious threat to human health with the advent of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). The urge to find novel drugs to deal with the appearance of drug-resistant TB and its variants is highly needed. This study a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Universiti Putra Malaysia Press
2022
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| Online Access: | http://psasir.upm.edu.my/id/eprint/100974/ http://psasir.upm.edu.my/id/eprint/100974/1/Discovery%20of%20Mycobacterium%20tuberculosis%20.pdf |
| _version_ | 1848863461109399552 |
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| author | El Moudaka, Tarek Murugan, Priya Abdul Rahman, Mohd Basyaruddin Tejo, Bimo Ario |
| author_facet | El Moudaka, Tarek Murugan, Priya Abdul Rahman, Mohd Basyaruddin Tejo, Bimo Ario |
| author_sort | El Moudaka, Tarek |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Tuberculosis (TB) remains a serious threat to human health with the advent of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). The urge to find novel drugs to deal with the appearance of drug-resistant TB and its variants is highly needed. This study aims to find new CYP121 inhibitors by screening 8,773 compounds from the drug repositioning database RepoDB. The selection of CYP121 potential inhibitors was based on two criteria: the new inhibitor should bind to CYP121 with higher affinity than its original ligand and interact with catalytically important residues for the function of CYP121. The ligands were docked onto CYP121 using AutoDock Vina, and the molecular dynamics simulation of the selected ligand was conducted using YASARA Structure. We found that antrafenine, an anti-inflammatory and analgesic agent with high CYP inhibitory promiscuity, was bound to CYP121 with a binding affinity of -12.6 kcal/mol and interacted with important residues at the CYP121 binding site. Molecular dynamics analysis of CYP121 bound to the original ligand and antrafenine showed that both ligands affected the dynamics of residues located distantly from the active site. Antrafenine caused more structural changes to CYP121 than the original ligand, as indicated by a significantly higher number of affected residues and rigid body movements caused by the binding of antrafenine to CYP121. |
| first_indexed | 2025-11-15T13:33:17Z |
| format | Article |
| id | upm-100974 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T13:33:17Z |
| publishDate | 2022 |
| publisher | Universiti Putra Malaysia Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1009742023-07-13T07:44:56Z http://psasir.upm.edu.my/id/eprint/100974/ Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing El Moudaka, Tarek Murugan, Priya Abdul Rahman, Mohd Basyaruddin Tejo, Bimo Ario Tuberculosis (TB) remains a serious threat to human health with the advent of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). The urge to find novel drugs to deal with the appearance of drug-resistant TB and its variants is highly needed. This study aims to find new CYP121 inhibitors by screening 8,773 compounds from the drug repositioning database RepoDB. The selection of CYP121 potential inhibitors was based on two criteria: the new inhibitor should bind to CYP121 with higher affinity than its original ligand and interact with catalytically important residues for the function of CYP121. The ligands were docked onto CYP121 using AutoDock Vina, and the molecular dynamics simulation of the selected ligand was conducted using YASARA Structure. We found that antrafenine, an anti-inflammatory and analgesic agent with high CYP inhibitory promiscuity, was bound to CYP121 with a binding affinity of -12.6 kcal/mol and interacted with important residues at the CYP121 binding site. Molecular dynamics analysis of CYP121 bound to the original ligand and antrafenine showed that both ligands affected the dynamics of residues located distantly from the active site. Antrafenine caused more structural changes to CYP121 than the original ligand, as indicated by a significantly higher number of affected residues and rigid body movements caused by the binding of antrafenine to CYP121. Universiti Putra Malaysia Press 2022-03-31 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/100974/1/Discovery%20of%20Mycobacterium%20tuberculosis%20.pdf El Moudaka, Tarek and Murugan, Priya and Abdul Rahman, Mohd Basyaruddin and Tejo, Bimo Ario (2022) Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing. Pertanika Journal of Science & Technology, 31 (3). art. no. 21. pp. 1503-1521. ISSN 0128-7680; ESSN: 2231-8526 http://www.pertanika.upm.edu.my/pjst/browse/regular-issue?article=JST-3830-2022 10.47836/pjst.31.3.21 |
| spellingShingle | El Moudaka, Tarek Murugan, Priya Abdul Rahman, Mohd Basyaruddin Tejo, Bimo Ario Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing |
| title | Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing |
| title_full | Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing |
| title_fullStr | Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing |
| title_full_unstemmed | Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing |
| title_short | Discovery of Mycobacterium tuberculosis CYP121 new inhibitor via structure-based drug repurposing |
| title_sort | discovery of mycobacterium tuberculosis cyp121 new inhibitor via structure-based drug repurposing |
| url | http://psasir.upm.edu.my/id/eprint/100974/ http://psasir.upm.edu.my/id/eprint/100974/ http://psasir.upm.edu.my/id/eprint/100974/ http://psasir.upm.edu.my/id/eprint/100974/1/Discovery%20of%20Mycobacterium%20tuberculosis%20.pdf |