Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment
Background and Aim: One of the ways to control high blood pressure is to deactivate the renin-angiotensinogen-aldosterone RAAS system. Renin, also known as angiotensinogenase,It is a type of enzyme that is produced in the afferent arterioles of the kidney by special cells called juxtaglomerular cell...
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Tehran University of Medical Sciences
2024-11-01
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| Online Access: | http://payavard.tums.ac.ir/article-1-7379-en.pdf |
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| author | Saeed Pirmoradi |
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| description | Background and Aim: One of the ways to control high blood pressure is to deactivate the renin-angiotensinogen-aldosterone RAAS system. Renin, also known as angiotensinogenase,It is a type of enzyme that is produced in the afferent arterioles of the kidney by special cells called juxtaglomerular cells and secreted into the bloodstream and converts angiotensinogen protein into angiotensin type 1, which is very effective in causing high blood pressure. Inhibition of renin as the rate-limiting step of this cycle is an effective way to stop it, which plays a role in the treatment of some diseases related to the heart and blood vessels and blood pressure. The purpose of this study is to use new and different methods based on software to discover newer medicinal compounds with less side effects and cost and in a shorter time to discover based on a reference drug for the treatment and control of blood pressure disease.
Materials and Methods: By selecting the inhibitory reference compound of renin enzyme by bioinformatics tools such as PHARMIT, ZINCPHARMER during virtual search through the structural and pharmacophoretic properties of the reference inhibitory compound, a number of new ligands were obtained. Then the docking process was performed and the selected top ligands in terms of toxicity, allergy, toxicity and ADME prediction were examined with the help of tools such as molsoft, PKCSM, way2drug and swiss ADME.
Results: Among the four final top ligands obtained, one of the ligands had the most interaction with different residues and with a higher docking binding energy (vina score=-9.7) than the others, and then the other two ligands had a favorable binding energy.Among the effective interacting residues, Asp215, Asp32 and Leu114 were bound to renin enzyme in superior ligands, such as the reference compound.
Conclusion: In general, the selected inhibitory ligands showed a good ability to interact with residues involved in substrate selectivity and catalytic activity and inhibition of renin enzyme activity according to the analysis of bioinformatics tools and their confirmation requires clinical studies. |
| format | Article |
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| issn | 1735-8132 2008-2665 |
| language | fas |
| publishDate | 2024-11-01 |
| publisher | Tehran University of Medical Sciences |
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| series | پیاورد سلامت |
| spelling | doaj-art-e64552578beb497da64a7f1c8a98de772025-08-20T03:09:16ZfasTehran University of Medical Sciencesپیاورد سلامت1735-81322008-26652024-11-01185429439Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and TreatmentSaeed Pirmoradi0 Ph.D. in Biochemistry, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran Background and Aim: One of the ways to control high blood pressure is to deactivate the renin-angiotensinogen-aldosterone RAAS system. Renin, also known as angiotensinogenase,It is a type of enzyme that is produced in the afferent arterioles of the kidney by special cells called juxtaglomerular cells and secreted into the bloodstream and converts angiotensinogen protein into angiotensin type 1, which is very effective in causing high blood pressure. Inhibition of renin as the rate-limiting step of this cycle is an effective way to stop it, which plays a role in the treatment of some diseases related to the heart and blood vessels and blood pressure. The purpose of this study is to use new and different methods based on software to discover newer medicinal compounds with less side effects and cost and in a shorter time to discover based on a reference drug for the treatment and control of blood pressure disease. Materials and Methods: By selecting the inhibitory reference compound of renin enzyme by bioinformatics tools such as PHARMIT, ZINCPHARMER during virtual search through the structural and pharmacophoretic properties of the reference inhibitory compound, a number of new ligands were obtained. Then the docking process was performed and the selected top ligands in terms of toxicity, allergy, toxicity and ADME prediction were examined with the help of tools such as molsoft, PKCSM, way2drug and swiss ADME. Results: Among the four final top ligands obtained, one of the ligands had the most interaction with different residues and with a higher docking binding energy (vina score=-9.7) than the others, and then the other two ligands had a favorable binding energy.Among the effective interacting residues, Asp215, Asp32 and Leu114 were bound to renin enzyme in superior ligands, such as the reference compound. Conclusion: In general, the selected inhibitory ligands showed a good ability to interact with residues involved in substrate selectivity and catalytic activity and inhibition of renin enzyme activity according to the analysis of bioinformatics tools and their confirmation requires clinical studies.http://payavard.tums.ac.ir/article-1-7379-en.pdfblood pressurerenininhibitordocking |
| spellingShingle | Saeed Pirmoradi Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment پیاورد سلامت blood pressure renin inhibitor docking |
| title | Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment |
| title_full | Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment |
| title_fullStr | Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment |
| title_full_unstemmed | Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment |
| title_short | Design of New Inhibitory ligands Based on Bioenformatic Pharmacophore Modeling in Renin Enzyme for Blood Pressure Control and Treatment |
| title_sort | design of new inhibitory ligands based on bioenformatic pharmacophore modeling in renin enzyme for blood pressure control and treatment |
| topic | blood pressure renin inhibitor docking |
| url | http://payavard.tums.ac.ir/article-1-7379-en.pdf |
| work_keys_str_mv | AT saeedpirmoradi designofnewinhibitoryligandsbasedonbioenformaticpharmacophoremodelinginreninenzymeforbloodpressurecontrolandtreatment |