Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy
Topomer comparative molecular field analysis (topomer CoMFA) is applied to the quantitative structure-activity relationship (QSAR) study of aminomethylenethiophene (AMT) derivatives as lysyl oxidase (LOX) inhibitors. A total of thirty-six AMT derivatives were selected to build the QSAR model. The es...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2020/2036585 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832566208881229824 |
|---|---|
| author | Jing Han Guochao Yan Jianping Feng Xianglin Yang Yuan Zhou |
| author_facet | Jing Han Guochao Yan Jianping Feng Xianglin Yang Yuan Zhou |
| author_sort | Jing Han |
| collection | DOAJ |
| description | Topomer comparative molecular field analysis (topomer CoMFA) is applied to the quantitative structure-activity relationship (QSAR) study of aminomethylenethiophene (AMT) derivatives as lysyl oxidase (LOX) inhibitors. A total of thirty-six AMT derivatives were selected to build the QSAR model. The established topomer CoMFA model has the non-cross-validated correlation coefficient (r2) of 0.912 and the leave-one-out correlation coefficient (q2) of 0.540, which is statistically significant. The theoretically predicted anti-LOX potency agrees well with the experimentally observed inhibitory activity, proving the reasonable predictive ability of the QSAR model. The effect of molecular field information on the LOX inhibition of substituted aminomethylenethiophene was discussed in detail. The structural modification of the aminomethylenethiophene scaffold was carried out, and novel AMT derivatives with theoretically decent LOX inhibition were proposed. The topomer CoMFA modeling could provide a quantitative perspective into the structure-activity relationship of AMT derivatives and potentially speed up the rational design of LOX inhibitors as antimetastatic agents for cancer therapy. |
| format | Article |
| id | doaj-art-5e5913dacb844c5b800e723e4ac5cce5 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-5e5913dacb844c5b800e723e4ac5cce52025-02-03T01:04:46ZengWileyJournal of Chemistry2090-90632090-90712020-01-01202010.1155/2020/20365852036585Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer TherapyJing Han0Guochao Yan1Jianping Feng2Xianglin Yang3Yuan Zhou4Department of Electronic and Information Engineering, Changsha Social Work College, Changsha 410004, Hunan, ChinaCollege of Mining Engineering, Taiyuan University of Technology, Taiyuan, Shanxi, ChinaCollege of Mining Engineering, Taiyuan University of Technology, Taiyuan, Shanxi, ChinaWestern Australia School of Mines: Minerals, Energy and Chemical Engineering, Curtin University, Kalgoorlie, WA 6430, AustraliaCollege of Chemistry and Chemical Engineering, Hunan Institute of Engineering, Xiangtan 411104, Hunan, ChinaTopomer comparative molecular field analysis (topomer CoMFA) is applied to the quantitative structure-activity relationship (QSAR) study of aminomethylenethiophene (AMT) derivatives as lysyl oxidase (LOX) inhibitors. A total of thirty-six AMT derivatives were selected to build the QSAR model. The established topomer CoMFA model has the non-cross-validated correlation coefficient (r2) of 0.912 and the leave-one-out correlation coefficient (q2) of 0.540, which is statistically significant. The theoretically predicted anti-LOX potency agrees well with the experimentally observed inhibitory activity, proving the reasonable predictive ability of the QSAR model. The effect of molecular field information on the LOX inhibition of substituted aminomethylenethiophene was discussed in detail. The structural modification of the aminomethylenethiophene scaffold was carried out, and novel AMT derivatives with theoretically decent LOX inhibition were proposed. The topomer CoMFA modeling could provide a quantitative perspective into the structure-activity relationship of AMT derivatives and potentially speed up the rational design of LOX inhibitors as antimetastatic agents for cancer therapy.http://dx.doi.org/10.1155/2020/2036585 |
| spellingShingle | Jing Han Guochao Yan Jianping Feng Xianglin Yang Yuan Zhou Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy Journal of Chemistry |
| title | Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy |
| title_full | Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy |
| title_fullStr | Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy |
| title_full_unstemmed | Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy |
| title_short | Using Topomer Comparative Molecular Field Analysis to Elucidate Activity Differences of Aminomethylenethiophene Derivatives as Lysyl Oxidase Inhibitors: Implications for Rational Design of Antimetastatic Agents for Cancer Therapy |
| title_sort | using topomer comparative molecular field analysis to elucidate activity differences of aminomethylenethiophene derivatives as lysyl oxidase inhibitors implications for rational design of antimetastatic agents for cancer therapy |
| url | http://dx.doi.org/10.1155/2020/2036585 |
| work_keys_str_mv | AT jinghan usingtopomercomparativemolecularfieldanalysistoelucidateactivitydifferencesofaminomethylenethiophenederivativesaslysyloxidaseinhibitorsimplicationsforrationaldesignofantimetastaticagentsforcancertherapy AT guochaoyan usingtopomercomparativemolecularfieldanalysistoelucidateactivitydifferencesofaminomethylenethiophenederivativesaslysyloxidaseinhibitorsimplicationsforrationaldesignofantimetastaticagentsforcancertherapy AT jianpingfeng usingtopomercomparativemolecularfieldanalysistoelucidateactivitydifferencesofaminomethylenethiophenederivativesaslysyloxidaseinhibitorsimplicationsforrationaldesignofantimetastaticagentsforcancertherapy AT xianglinyang usingtopomercomparativemolecularfieldanalysistoelucidateactivitydifferencesofaminomethylenethiophenederivativesaslysyloxidaseinhibitorsimplicationsforrationaldesignofantimetastaticagentsforcancertherapy AT yuanzhou usingtopomercomparativemolecularfieldanalysistoelucidateactivitydifferencesofaminomethylenethiophenederivativesaslysyloxidaseinhibitorsimplicationsforrationaldesignofantimetastaticagentsforcancertherapy |