Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders
Background : Human carbonic anhydrases (CAs) play a role in various pathological mechanisms by controlling intracellular and extracellular pH balance. Irregular expression and function of CAs have been associated with multiple human diseases, such as obesity, cancer, glaucoma, and epilepsy. In this...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Korean Society for the Study of Obesity
2023-09-01
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| Series: | Journal of Obesity & Metabolic Syndrome |
| Subjects: | |
| Online Access: | http://www.jomes.org/journal/view.html?doi=10.7570/jomes23029 |
| _version_ | 1827805875573620736 |
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| author | Ebrahim Yarmohammadi Maryam Khanjani Zahra Khamverdi Marzieh Savari Amir Taherkhani |
| author_facet | Ebrahim Yarmohammadi Maryam Khanjani Zahra Khamverdi Marzieh Savari Amir Taherkhani |
| author_sort | Ebrahim Yarmohammadi |
| collection | DOAJ |
| description | Background : Human carbonic anhydrases (CAs) play a role in various pathological mechanisms by controlling intracellular and extracellular pH balance. Irregular expression and function of CAs have been associated with multiple human diseases, such as obesity, cancer, glaucoma, and epilepsy. In this work, we identify herbal compounds that are potential inhibitors of CA VI. Methods : We used the AutoDock tool to evaluate binding affinity between the CA VI active site and 79 metabolites derived from flavonoids, anthraquinones, or cinnamic acids. Compounds ranked at the top were chosen for molecular dynamics (MD) simulations. Interactions between the best CA VI inhibitors and residues within the CA VI active site were examined before and after MD analysis. Additionally, the effects of the most potent CA VI inhibitor on cell viability were ascertained in vitro through the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results : Kaempferol 3-rutinoside-4-glucoside, orientin, kaempferol 3-rutinoside-7-sophoroside, cynarin, and chlorogenic acid were estimated to establish binding with the CA VI catalytic domain at the picomolar scale. The range of root mean square deviations for CA VI complexes with kaempferol 3-rutinoside-4-glucoside, aloe-emodin 8-glucoside, and cynarin was 1.37 to 2.05, 1.25 to 1.85, and 1.07 to 1.54 Å, respectively. The MTT assay results demonstrated that cynarin had a substantial effect on HCT-116 cell viability. Conclusion : This study identified several herbal compounds that could be potential drug candidates for inhibiting CA VI. |
| first_indexed | 2024-03-11T21:33:28Z |
| format | Article |
| id | doaj.art-045f8aecfb244478b5de108f2e22cf3c |
| institution | Directory Open Access Journal |
| issn | 2508-6235 |
| language | English |
| last_indexed | 2024-03-11T21:33:28Z |
| publishDate | 2023-09-01 |
| publisher | Korean Society for the Study of Obesity |
| record_format | Article |
| series | Journal of Obesity & Metabolic Syndrome |
| spelling | doaj.art-045f8aecfb244478b5de108f2e22cf3c2023-09-27T05:37:08ZengKorean Society for the Study of ObesityJournal of Obesity & Metabolic Syndrome2508-62352023-09-0132324725810.7570/jomes23029jomes23029Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic DisordersEbrahim Yarmohammadi0Maryam Khanjani1Zahra Khamverdi2Marzieh Savari3Amir Taherkhani4Department of Restorative Dentistry, School of Dentistry, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Restorative Dentistry, School of Dentistry, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, IranDepartment of Restorative Dentistry, School of Dentistry, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, IranResearch Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, IranResearch Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, IranBackground : Human carbonic anhydrases (CAs) play a role in various pathological mechanisms by controlling intracellular and extracellular pH balance. Irregular expression and function of CAs have been associated with multiple human diseases, such as obesity, cancer, glaucoma, and epilepsy. In this work, we identify herbal compounds that are potential inhibitors of CA VI. Methods : We used the AutoDock tool to evaluate binding affinity between the CA VI active site and 79 metabolites derived from flavonoids, anthraquinones, or cinnamic acids. Compounds ranked at the top were chosen for molecular dynamics (MD) simulations. Interactions between the best CA VI inhibitors and residues within the CA VI active site were examined before and after MD analysis. Additionally, the effects of the most potent CA VI inhibitor on cell viability were ascertained in vitro through the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results : Kaempferol 3-rutinoside-4-glucoside, orientin, kaempferol 3-rutinoside-7-sophoroside, cynarin, and chlorogenic acid were estimated to establish binding with the CA VI catalytic domain at the picomolar scale. The range of root mean square deviations for CA VI complexes with kaempferol 3-rutinoside-4-glucoside, aloe-emodin 8-glucoside, and cynarin was 1.37 to 2.05, 1.25 to 1.85, and 1.07 to 1.54 Å, respectively. The MTT assay results demonstrated that cynarin had a substantial effect on HCT-116 cell viability. Conclusion : This study identified several herbal compounds that could be potential drug candidates for inhibiting CA VI.http://www.jomes.org/journal/view.html?doi=10.7570/jomes23029anthraquinonesneoplasmscarbonic anhydrasescinnamic acidflavonoidsinhibitorobesity |
| spellingShingle | Ebrahim Yarmohammadi Maryam Khanjani Zahra Khamverdi Marzieh Savari Amir Taherkhani Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders Journal of Obesity & Metabolic Syndrome anthraquinones neoplasms carbonic anhydrases cinnamic acid flavonoids inhibitor obesity |
| title | Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders |
| title_full | Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders |
| title_fullStr | Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders |
| title_full_unstemmed | Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders |
| title_short | Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders |
| title_sort | herbal metabolites as potential carbonic anhydrase inhibitors promising compounds for cancer and metabolic disorders |
| topic | anthraquinones neoplasms carbonic anhydrases cinnamic acid flavonoids inhibitor obesity |
| url | http://www.jomes.org/journal/view.html?doi=10.7570/jomes23029 |
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