Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents
Cancer remains one of the deadliest diseases worldwide, and currently cancer treatment is facing several problems related to adverse effects and drug resistance. To address these problems, new prospective anticancer medications are required. Natural compounds, which have been extensively used in the...
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| Format: | Article |
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Agency for the Assessment and Application of Technology (BPPT), Indonesia
2023
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| _version_ | 1825939515888369664 |
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| author | Wibowo, Aji Waluyo, Danang Ario Tejo, Bimo Komariyah, Tinta Yandwiputra Besari, Ariza Endang Prabandari, Erwahyuni |
| author_facet | Wibowo, Aji Waluyo, Danang Ario Tejo, Bimo Komariyah, Tinta Yandwiputra Besari, Ariza Endang Prabandari, Erwahyuni |
| author_sort | Wibowo, Aji |
| collection | UPM |
| description | Cancer remains one of the deadliest diseases worldwide, and currently cancer treatment is facing several problems related to adverse effects and drug resistance. To address these problems, new prospective anticancer medications are required. Natural compounds, which have been extensively used in the drug research, including for the treatment of cancer, are emerging as viable candidates. This study aimed to evaluate 33 in-house natural compounds against dihydroorotate dehydrogenase (DHODH) enzyme, a viable target to develop anticancer agent, and to analyze the hit inhibitory mechanism against protein target. In the activity assay, atovaquone was the sole substance to have activity against DHODH, with an inhibition rate of 47.44 at 10 µM. However, discrepancies were shown in the molecular docking result, where atovaquone were identified as hits. Molecular dynamic analysis revealed that atovaquone initially bound to the active site before being forced to the outside due to cleavage of hydrogen bond between the ligand and responsible residue. This study clearly demonstrated the importance of molecular dynamic analysis to study inhibitory mechanism of compound against target protein that may be useful for further development. |
| first_indexed | 2024-12-09T02:19:40Z |
| format | Article |
| id | upm.eprints-107764 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2024-12-09T02:19:40Z |
| publishDate | 2023 |
| publisher | Agency for the Assessment and Application of Technology (BPPT), Indonesia |
| record_format | dspace |
| spelling | upm.eprints-1077642024-10-28T06:10:14Z http://psasir.upm.edu.my/id/eprint/107764/ Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents Wibowo, Aji Waluyo, Danang Ario Tejo, Bimo Komariyah, Tinta Yandwiputra Besari, Ariza Endang Prabandari, Erwahyuni Cancer remains one of the deadliest diseases worldwide, and currently cancer treatment is facing several problems related to adverse effects and drug resistance. To address these problems, new prospective anticancer medications are required. Natural compounds, which have been extensively used in the drug research, including for the treatment of cancer, are emerging as viable candidates. This study aimed to evaluate 33 in-house natural compounds against dihydroorotate dehydrogenase (DHODH) enzyme, a viable target to develop anticancer agent, and to analyze the hit inhibitory mechanism against protein target. In the activity assay, atovaquone was the sole substance to have activity against DHODH, with an inhibition rate of 47.44 at 10 µM. However, discrepancies were shown in the molecular docking result, where atovaquone were identified as hits. Molecular dynamic analysis revealed that atovaquone initially bound to the active site before being forced to the outside due to cleavage of hydrogen bond between the ligand and responsible residue. This study clearly demonstrated the importance of molecular dynamic analysis to study inhibitory mechanism of compound against target protein that may be useful for further development. Agency for the Assessment and Application of Technology (BPPT), Indonesia 2023-12-07 Article PeerReviewed Wibowo, Aji and Waluyo, Danang and Ario Tejo, Bimo and Komariyah, Tinta and Yandwiputra Besari, Ariza and Endang Prabandari, Erwahyuni (2023) Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents. Jurnal Bioteknologi & Biosains Indonesia, 10 (2). pp. 174-202. ISSN 2548 –611X https://ejournal.brin.go.id/JBBI/article/view/2842 |
| spellingShingle | Wibowo, Aji Waluyo, Danang Ario Tejo, Bimo Komariyah, Tinta Yandwiputra Besari, Ariza Endang Prabandari, Erwahyuni Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents |
| title | Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents |
| title_full | Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents |
| title_fullStr | Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents |
| title_full_unstemmed | Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents |
| title_short | Evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti-cancer agents |
| title_sort | evaluation and inhibitory mechanism analysis of natural compounds againts dihydroorotate dehydrogenase as anti cancer agents |
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