Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening
Shih-Hung Lin,1 Kao-Jean Huang,1,2 Ching-Feng Weng,1 David Shiuan1 1Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 2Development Center of Biotechnology, Taipei, Taiwan, Republic of China Abstract: Cholesterol plays an im...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-06-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/exploration-of-natural-product-ingredients-as-inhibitors-of-human-hmg--peer-reviewed-article-DDDT |
| _version_ | 1818194110823006208 |
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| author | Lin SH Huang KJ Weng CF Shiuan D |
| author_facet | Lin SH Huang KJ Weng CF Shiuan D |
| author_sort | Lin SH |
| collection | DOAJ |
| description | Shih-Hung Lin,1 Kao-Jean Huang,1,2 Ching-Feng Weng,1 David Shiuan1 1Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 2Development Center of Biotechnology, Taipei, Taiwan, Republic of China Abstract: Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR). The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank) database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity) properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration) values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening. Keywords: HMG-CoA reductase, virtual screening, curcumin, salvianolic acid C |
| first_indexed | 2024-12-12T00:57:05Z |
| format | Article |
| id | doaj.art-065ca4b01a3645309efd557450df97cd |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-12T00:57:05Z |
| publishDate | 2015-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-065ca4b01a3645309efd557450df97cd2022-12-22T00:43:51ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-06-012015default3313332422335Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screeningLin SHHuang KJWeng CFShiuan DShih-Hung Lin,1 Kao-Jean Huang,1,2 Ching-Feng Weng,1 David Shiuan1 1Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, Republic of China; 2Development Center of Biotechnology, Taipei, Taiwan, Republic of China Abstract: Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR). The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank) database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity) properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration) values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening. Keywords: HMG-CoA reductase, virtual screening, curcumin, salvianolic acid Chttp://www.dovepress.com/exploration-of-natural-product-ingredients-as-inhibitors-of-human-hmg--peer-reviewed-article-DDDT |
| spellingShingle | Lin SH Huang KJ Weng CF Shiuan D Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening Drug Design, Development and Therapy |
| title | Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening |
| title_full | Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening |
| title_fullStr | Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening |
| title_full_unstemmed | Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening |
| title_short | Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening |
| title_sort | exploration of natural product ingredients as inhibitors of human hmg coa reductase through structure based virtual screening |
| url | http://www.dovepress.com/exploration-of-natural-product-ingredients-as-inhibitors-of-human-hmg--peer-reviewed-article-DDDT |
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