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Computational guided designing of novel Renin inhibitors
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| Author:
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K.RAMYA , R. SURESH, HONNAVALLI YOGISH KUMAR
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| Abstract:
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Renin-angiotensin-aldosterone-system (RAAS) inhibitors play an incredible role in the pathophysiology of heart failure, diabetic nephropathy, Myocardial infarction and Hypertension. Renin inhibitors obstruct the foremost step in the RAAS cascade. Renin inhibitors play a valuable part in the regulation of blood pressure by obstructing the actions of renin enzyme. Circulating renin enzyme hydrolyses Angiotensinogen to angiotensin I (Ang I), which is further breakdown to angiotensin II (Ang II) by the angiotensin converting enzyme (ACE). Angiotensin II is the prime module to root the elevation of blood pressure. In 2007, Aliskiren, Direct renin inhibitor discovered by computational tools, emerged as an experimental drug and officially approved by the US FDA. Aliskiren indicated average to superior efficiency with minor contrary effects virtual to other RAAS inhibitors. Conversely, it suffers from very poor oral bioavailability of less than 2%. Thus, it is prerequisite for innovation of novel renin inhibitors with improved ADME properties and efficiency. Current study describes approach of structure-based virtual screening for the innovation of novel renin inhibitors. We have achieved molecular dynamics simulation studies to recognize significant interacting topographies of aliskiren along with water dynamics in the dynamic spots. Notorious topographies were engaged to accomplish virtual screen against the external library. The Hits are authorized on the basis of interaction patterns. Furthermore, the authorized hits drive for synthesis and verified against renin enzyme inhibition and lowering of blood pressure in hypertensive animal models.
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| Keyword:
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Aliskiren, Docking, Hypertension, Molecular Dynamic simulation, Renin, Virtual screening.
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| EOI:
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-
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| DOI:
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https://doi.org/10.31838/ijpr/2020.SP3.061
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| Download:
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