| Autor: |
Ghanta, Prasanth, Sinha, Shweta, Doble, Mukesh, Ramaiah, Basavaraju |
| Zdroj: |
Journal of Biomolecular Structure and Dynamics; April 2022, Vol. 40 Issue: 6 p2785-2796, 12p |
| Abstrakt: |
AbstractInflammation plays a major role in the onset and progression of many diseases related to the respiratory system. Cysteinyl leukotrienes, the products of 5-LOX are a potent bronchoconstrictor. Vasicine, vasicinone and deoxyvasicine are the pyrroquinazoline alkaloids of Adhatoda vasicathat are well known for their bronchodilatory activity. The current investigation evaluates the 5-LOX inhibitory potential of these alkaloids. Molecular docking results indicated that these alkaloids have similar binding energy as that of Zileuton, a commercial drug. Analysis of the molecular dynamics simulations, the binding free energy derived from MM-PBSA and interaction entropy indicated that vasicinone (-8.33 kcal/mol) exhibited a binding free energy comparable to that of Zileuton (-8.52 kcal/mol). The in-vitro results indicate the potential of vasicinone as a competitive inhibitor, while the in-silico results highlighted the potential of vasicine and deoxyvasicine as allosteric inhibitors. A possible mechanism behind the activity exhibited by the plant was also determined, which emphasized the potential of these alkaloids as leads for the design of novel 5-LOX inhibitors |
| Databáze: |
Supplemental Index |
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