Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold
The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimenta...
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| Format: | Article |
| Language: | English |
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Sciendo
2021-03-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0005 |
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| author | Al-Shar’i Nizar A. Al-Balas Qosay A. Hassan Mohammad A. El-Elimat Tamam M. Aljabal Ghazi A. Almaaytah Ammar M. |
| author_facet | Al-Shar’i Nizar A. Al-Balas Qosay A. Hassan Mohammad A. El-Elimat Tamam M. Aljabal Ghazi A. Almaaytah Ammar M. |
| author_sort | Al-Shar’i Nizar A. |
| collection | DOAJ |
| description | The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction via its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors via computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization. |
| format | Article |
| id | doaj-art-e091c6c4b5554772b51df0a32144250c |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-e091c6c4b5554772b51df0a32144250c2025-02-02T11:49:57ZengSciendoActa Pharmaceutica1846-95582021-03-0171111513010.2478/acph-2021-0005acph-2021-0005Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffoldAl-Shar’i Nizar A.0Al-Balas Qosay A.1Hassan Mohammad A.2El-Elimat Tamam M.3Aljabal Ghazi A.4Almaaytah Ammar M.5Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030 Irbid 22110, JordanDepartment of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030 Irbid 22110, JordanDepartment of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030 Irbid 22110, JordanDepartment of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030 Irbid 22110, JordanDepartment of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030 Irbid 22110, JordanDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, JordanThe glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction via its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors via computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization.https://doi.org/10.2478/acph-2021-0005ellagic acidglyoxalase-izinc-bindinganticancermolecular dockingmm-gbmv |
| spellingShingle | Al-Shar’i Nizar A. Al-Balas Qosay A. Hassan Mohammad A. El-Elimat Tamam M. Aljabal Ghazi A. Almaaytah Ammar M. Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold Acta Pharmaceutica ellagic acid glyoxalase-i zinc-binding anticancer molecular docking mm-gbmv |
| title | Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold |
| title_full | Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold |
| title_fullStr | Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold |
| title_full_unstemmed | Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold |
| title_short | Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold |
| title_sort | ellagic acid a potent glyoxalase i inhibitor with a unique scaffold |
| topic | ellagic acid glyoxalase-i zinc-binding anticancer molecular docking mm-gbmv |
| url | https://doi.org/10.2478/acph-2021-0005 |
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