Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors
In this work, a 3D-QSAR model involving for 40 dipeptidyl boronic acid proteasome inhibitors was built based on Topomer CoMFA. The multiple correlation coefficient of fitting, cross-validation and external validation were 0.908, 0.647 and 0.703, respectively. The results indicated that the obtained...
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| Format: | Article |
| Language: | English |
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Serbian Chemical Society
2017-01-01
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| Series: | Journal of the Serbian Chemical Society |
| Subjects: | |
| Online Access: | http://www.doiserbia.nb.rs/img/doi/0352-5139/2017/0352-51391700047T.pdf |
| _version_ | 1811249853544529920 |
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| author | Tong Jian-Bo Li Yuan-Yuan Jiang Guo-Yan Li Kang-Nan |
| author_facet | Tong Jian-Bo Li Yuan-Yuan Jiang Guo-Yan Li Kang-Nan |
| author_sort | Tong Jian-Bo |
| collection | DOAJ |
| description | In this work, a 3D-QSAR model involving for 40 dipeptidyl boronic acid proteasome inhibitors was built based on Topomer CoMFA. The multiple correlation coefficient of fitting, cross-validation and external validation were 0.908, 0.647 and 0.703, respectively. The results indicated that the obtained Topomer CoMFA model has not only the favourable estimation stability but also the good prediction capability. Topomer Search was employed as a tool for virtual screening in lead-like compounds of ZINC database. Finally, 1 R1 group, 7 R2 groups and 6 R3 groups with higher contribution values were employed to alternately substitute the R1, R2 and R3 of the templete compound 23 with highest bioactivity. As a consequence, 33 new molecules with higher activity than that of the model molecule were designed successfully. The results showed that the Topomer Search technology could be effectively apply to screen and design new dipeptidyl boronic acid proteasome inhibitors and has good predictive capability to design new dipeptidyl boronic acid proteasome inhibitors drugs as guidance. |
| first_indexed | 2024-04-12T15:53:43Z |
| format | Article |
| id | doaj.art-3195d6064a104bd486cf7bc46fd8b636 |
| institution | Directory Open Access Journal |
| issn | 0352-5139 1820-7421 |
| language | English |
| last_indexed | 2024-04-12T15:53:43Z |
| publishDate | 2017-01-01 |
| publisher | Serbian Chemical Society |
| record_format | Article |
| series | Journal of the Serbian Chemical Society |
| spelling | doaj.art-3195d6064a104bd486cf7bc46fd8b6362022-12-22T03:26:25ZengSerbian Chemical SocietyJournal of the Serbian Chemical Society0352-51391820-74212017-01-018291025103710.2298/JSC161227047T0352-51391700047TApplication of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitorsTong Jian-Bo0Li Yuan-Yuan1Jiang Guo-Yan2Li Kang-Nan3Shaanxi University of Science and Technology, College of Chemistry and Chemical Engineering, Xi’an, ChinaShaanxi University of Science and Technology, College of Chemistry and Chemical Engineering, Xi’an, ChinaShaanxi University of Science and Technology, College of Chemistry and Chemical Engineering, Xi’an, ChinaShaanxi University of Science and Technology, College of Chemistry and Chemical Engineering, Xi’an, ChinaIn this work, a 3D-QSAR model involving for 40 dipeptidyl boronic acid proteasome inhibitors was built based on Topomer CoMFA. The multiple correlation coefficient of fitting, cross-validation and external validation were 0.908, 0.647 and 0.703, respectively. The results indicated that the obtained Topomer CoMFA model has not only the favourable estimation stability but also the good prediction capability. Topomer Search was employed as a tool for virtual screening in lead-like compounds of ZINC database. Finally, 1 R1 group, 7 R2 groups and 6 R3 groups with higher contribution values were employed to alternately substitute the R1, R2 and R3 of the templete compound 23 with highest bioactivity. As a consequence, 33 new molecules with higher activity than that of the model molecule were designed successfully. The results showed that the Topomer Search technology could be effectively apply to screen and design new dipeptidyl boronic acid proteasome inhibitors and has good predictive capability to design new dipeptidyl boronic acid proteasome inhibitors drugs as guidance.http://www.doiserbia.nb.rs/img/doi/0352-5139/2017/0352-51391700047T.pdfquantitative structure-activity relationship (QSAR)proteasome inhibitorsTopomer CoMFATopomer searchdesign of new inhibitors |
| spellingShingle | Tong Jian-Bo Li Yuan-Yuan Jiang Guo-Yan Li Kang-Nan Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors Journal of the Serbian Chemical Society quantitative structure-activity relationship (QSAR) proteasome inhibitors Topomer CoMFA Topomer search design of new inhibitors |
| title | Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors |
| title_full | Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors |
| title_fullStr | Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors |
| title_full_unstemmed | Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors |
| title_short | Application of an R-group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors |
| title_sort | application of an r group search technique in the molecular design of dipeptidyl boronic acid proteasome inhibitors |
| topic | quantitative structure-activity relationship (QSAR) proteasome inhibitors Topomer CoMFA Topomer search design of new inhibitors |
| url | http://www.doiserbia.nb.rs/img/doi/0352-5139/2017/0352-51391700047T.pdf |
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