Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors
Transketolase (TKL) plays a key role in plant photosynthesis and has been predicted to be a potent herbicide target. Homology modeling and molecular dynamics simulation were used to construct a target protein model. A target-based virtual screening was developed to discover novel potential transketo...
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doaj-d716b85ae3f24168bbb3d36d9b27a3e92020-11-24T23:53:18ZengMDPI AGMolecules1420-30492018-08-01239211610.3390/molecules23092116molecules23092116Structure-Based Discovery and Synthesis of Potential Transketolase InhibitorsJingqian Huo0Bin Zhao1Zhe Zhang2Jihong Xing3Jinlin Zhang4Jingao Dong5Zhijin Fan6College of Plant Protection, Agricultural University of Hebei, Baoding 071001, ChinaState Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin 300071, ChinaCollege of Plant Protection, Agricultural University of Hebei, Baoding 071001, ChinaCollege of Life Science, Agricultural University of Hebei, Baoding 071000, ChinaCollege of Plant Protection, Agricultural University of Hebei, Baoding 071001, ChinaCollege of Plant Protection, Agricultural University of Hebei, Baoding 071001, ChinaState Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin 300071, ChinaTransketolase (TKL) plays a key role in plant photosynthesis and has been predicted to be a potent herbicide target. Homology modeling and molecular dynamics simulation were used to construct a target protein model. A target-based virtual screening was developed to discover novel potential transketolase inhibitors. Based on the receptor transketolase 1 and a target-based virtual screening combined with structural similarity, six new compounds were selected from the ZINC database. Among the structural leads, a new compound ZINC12007063 was identified as a novel inhibitor of weeds. Two novel series of carboxylic amide derivatives were synthesized, and their structures were rationally identified by NMR and HRMS. Biological evaluation of the herbicidal and antifungal activities indicated that the compounds 4u and 8h were the most potent herbicidal agents, and they also showed potent fungicidal activity with a relatively broad-spectrum. ZINC12007063 was identified as a lead compound of potential transketolase inhibitors, 4u and 8h which has the herbicidal and antifungal activities were synthesized based on ZINC12007063. This study lays a foundation for the discovery of new pesticides.http://www.mdpi.com/1420-3049/23/9/2116transketolasevirtual screeningamides derivativessynthesisbiological activity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jingqian Huo Bin Zhao Zhe Zhang Jihong Xing Jinlin Zhang Jingao Dong Zhijin Fan |
spellingShingle |
Jingqian Huo Bin Zhao Zhe Zhang Jihong Xing Jinlin Zhang Jingao Dong Zhijin Fan Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors Molecules transketolase virtual screening amides derivatives synthesis biological activity |
author_facet |
Jingqian Huo Bin Zhao Zhe Zhang Jihong Xing Jinlin Zhang Jingao Dong Zhijin Fan |
author_sort |
Jingqian Huo |
title |
Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors |
title_short |
Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors |
title_full |
Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors |
title_fullStr |
Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors |
title_full_unstemmed |
Structure-Based Discovery and Synthesis of Potential Transketolase Inhibitors |
title_sort |
structure-based discovery and synthesis of potential transketolase inhibitors |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-08-01 |
description |
Transketolase (TKL) plays a key role in plant photosynthesis and has been predicted to be a potent herbicide target. Homology modeling and molecular dynamics simulation were used to construct a target protein model. A target-based virtual screening was developed to discover novel potential transketolase inhibitors. Based on the receptor transketolase 1 and a target-based virtual screening combined with structural similarity, six new compounds were selected from the ZINC database. Among the structural leads, a new compound ZINC12007063 was identified as a novel inhibitor of weeds. Two novel series of carboxylic amide derivatives were synthesized, and their structures were rationally identified by NMR and HRMS. Biological evaluation of the herbicidal and antifungal activities indicated that the compounds 4u and 8h were the most potent herbicidal agents, and they also showed potent fungicidal activity with a relatively broad-spectrum. ZINC12007063 was identified as a lead compound of potential transketolase inhibitors, 4u and 8h which has the herbicidal and antifungal activities were synthesized based on ZINC12007063. This study lays a foundation for the discovery of new pesticides. |
topic |
transketolase virtual screening amides derivatives synthesis biological activity |
url |
http://www.mdpi.com/1420-3049/23/9/2116 |
work_keys_str_mv |
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