In silico approach for identification of potential tetracyclic triterpenoids from mushroom as HMG-CoA reductase inhibitor
Cardiovascular disease is estimated to be responsible for one-third of all global deaths annually. It occurs mostly due to hyperlipidemia, a condition where excessive cholesterol deposits in blood vessels. A favorable target for treating hyperlipidemia involves the crucial role of inhibition of a sp...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
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| Series: | Aspects of Molecular Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949688824000200 |
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| Summary: | Cardiovascular disease is estimated to be responsible for one-third of all global deaths annually. It occurs mostly due to hyperlipidemia, a condition where excessive cholesterol deposits in blood vessels. A favorable target for treating hyperlipidemia involves the crucial role of inhibition of a specific enzyme known as 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The primary goal of this present study is to identify potential HMG-CoA reductase inhibitors containing tetracyclic triterpene nucleus derived from mushrooms. A library of 86 myco-constituents bearing a tetracyclic triterpene scaffold was prepared and screened to identify potential HMG-CoA reductase inhibitors targeting proteins 1HW8 and 1HW9. For this purpose, molecular docking, ADME prediction, and molecular dynamics (MD) simulation studies were performed on this in-house prepared database. The virtual screening results exhibited M_02(c) as the best hit with promising SP Glide scores compared to standard statin drugs. In order to assess the stability and interactions, a 100 ns MD simulation was performed. Further, M_02(c) was also analysed for MMGBSA binding energy to access and validate the thermodynamic stability of the protein-ligand complex. The results of this study revealed that M_02(c) is a promising hit molecule and may emerge as a potent HMG-CoA reductase inhibitor in preventing and treating hyperlipidemia. |
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| ISSN: | 2949-6888 |