Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking
Capuramycin and a few semisynthetic derivatives have shown potential as anti-tuberculosis antibiotics.To understand their mechanism of action and structureactivity relationships a 3D-QSAR and molecular docking studies were performed. A set of 52 capuramycin derivatives for the training set and 13 fo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2017-12-01
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| Series: | Open Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/chem-2017-0039 |
| _version_ | 1818715960535678976 |
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| author | Jin Yuanyuan Fan Shuai Lv Guangxin Meng Haoyi Sun Zhengyang Jiang Wei Van Lanen Steven G. Yang Zhaoyong |
| author_facet | Jin Yuanyuan Fan Shuai Lv Guangxin Meng Haoyi Sun Zhengyang Jiang Wei Van Lanen Steven G. Yang Zhaoyong |
| author_sort | Jin Yuanyuan |
| collection | DOAJ |
| description | Capuramycin and a few semisynthetic derivatives have shown potential as anti-tuberculosis antibiotics.To understand their mechanism of action and structureactivity relationships a 3D-QSAR and molecular docking studies were performed. A set of 52 capuramycin derivatives for the training set and 13 for the validation set was used. A highly predictive MFA model was obtained with crossvalidated q2 of 0.398, and non-cross validated partial least-squares (PLS) analysis showed a conventional r2 of 0.976 and r2pred of 0.839. The model has an excellent predictive ability. Combining the 3D-QSAR and molecular docking studies, a number of new capuramycin analogs with predicted improved activities were designed. Biological activity tests of one analog showed useful antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Computer-aided molecular docking and 3D-QSAR can improve the design of new capuramycin antimycobacterial antibiotics. |
| first_indexed | 2024-12-17T19:11:40Z |
| format | Article |
| id | doaj.art-14fda7caeb5c40b6af19b2407e4cd548 |
| institution | Directory Open Access Journal |
| issn | 2391-5420 |
| language | English |
| last_indexed | 2024-12-17T19:11:40Z |
| publishDate | 2017-12-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Chemistry |
| spelling | doaj.art-14fda7caeb5c40b6af19b2407e4cd5482022-12-21T21:35:50ZengDe GruyterOpen Chemistry2391-54202017-12-0115129930710.1515/chem-2017-0039chem-2017-0039Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular dockingJin Yuanyuan0Fan Shuai1Lv Guangxin2Meng Haoyi3Sun Zhengyang4Jiang Wei5Van Lanen Steven G.6Yang Zhaoyong7Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536(USA)Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100050, People’s Republic of ChinaCapuramycin and a few semisynthetic derivatives have shown potential as anti-tuberculosis antibiotics.To understand their mechanism of action and structureactivity relationships a 3D-QSAR and molecular docking studies were performed. A set of 52 capuramycin derivatives for the training set and 13 for the validation set was used. A highly predictive MFA model was obtained with crossvalidated q2 of 0.398, and non-cross validated partial least-squares (PLS) analysis showed a conventional r2 of 0.976 and r2pred of 0.839. The model has an excellent predictive ability. Combining the 3D-QSAR and molecular docking studies, a number of new capuramycin analogs with predicted improved activities were designed. Biological activity tests of one analog showed useful antibiotic activity against Mycobacterium smegmatis MC2 155 and Mycobacterium tuberculosis H37Rv. Computer-aided molecular docking and 3D-QSAR can improve the design of new capuramycin antimycobacterial antibiotics.https://doi.org/10.1515/chem-2017-0039capuramycin analogueantimycobacterial3d-qsarmolecular dockingdrug design |
| spellingShingle | Jin Yuanyuan Fan Shuai Lv Guangxin Meng Haoyi Sun Zhengyang Jiang Wei Van Lanen Steven G. Yang Zhaoyong Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking Open Chemistry capuramycin analogue antimycobacterial 3d-qsar molecular docking drug design |
| title | Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking |
| title_full | Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking |
| title_fullStr | Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking |
| title_full_unstemmed | Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking |
| title_short | Computer-aided drug design of capuramycin analogues as anti-tuberculosis antibiotics by 3D-QSAR and molecular docking |
| title_sort | computer aided drug design of capuramycin analogues as anti tuberculosis antibiotics by 3d qsar and molecular docking |
| topic | capuramycin analogue antimycobacterial 3d-qsar molecular docking drug design |
| url | https://doi.org/10.1515/chem-2017-0039 |
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