scholarly journals Repurposing of Pharmaceutical Drugs by High-throughput Approach for Antihypertensive Activity as Inhibitors of Angiotensin-Converting Enzyme (ACE) Using HPLC-ESI-MS/MS Method

2021 ◽  
pp. 103279
Author(s):  
Muhammad Salman Bhatti ◽  
Khalid M. Alseud ◽  
Jalal Uddin ◽  
Hesham R. El-Seedi ◽  
Syed Ghulam Musharraf
2018 ◽  
Vol 32 (8) ◽  
pp. 1564-1573 ◽  
Author(s):  
Amani A. Awaad ◽  
Reham M. El-Meligy ◽  
Ghada M. Zain ◽  
Amal A. Safhi ◽  
Noura A. AL Qurain ◽  
...  

Author(s):  
ZOZIMUS DIVYA LOBO C ◽  
SYED MOHAMED A ◽  
GNANENDRA SHANMUGAM

Objective: The objective of this study was to investigate the antihypertensive activity of heterocyclic compounds against angiotensin-converting enzyme (ACE) through molecular docking studies. Methods: The X-ray crystal three-dimensional (3D) structure of human ACE complexed with lisinopril (PDB ID: 1O86) was retrieved from protein databank. The two-dimensional structures of 10 selected heterocyclic compounds were drawn in ACD-Chemsketch and converted into 3D structures. The 3D structures of compounds were virtually screened in the binding pockets of ACE using FlexX docking program. Further, the chemical entities revealing the molecular electronic structures of the best docked compound (Compound-4) were explored through density functional theory studies. Results: The Compound-4 showed the highest docking score of −26.6290 kJ/mol with ACE. The Hbond and non-bonded interactions are favored by phenylalanine, leucine, and arginine. The energy gap of 1.60 eV between highest occupied molecular orbital and lowest unoccupied molecular orbitals explained the presence of strong electron-acceptor group. Furthermore, the molecular electrostatic potential studies clearly envisaged the requirement of electropositive and electronegative groups are crucial for the ACE inhibitor activities. Conclusion: The identification of good ACE inhibitors requires the understanding of the current ACE inhibitors. Thus, the docking interactions of Compound-4 and its molecular electronic structure significantly imply its potential as antihypertensive agent. However, further clinical studies are required to ascertain its potential toxic effects.


2019 ◽  
Vol 13 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Huma Khan ◽  
Varun Jaiswal ◽  
Saurabh Kulshreshtha ◽  
Azhar Khan

Background: Hypertension is the chronic medical condition and it affected billions of people worldwide. Natural medicines are the main alternatives to treatment for a majority of people suffering from hypertension. Niazicin-A, Niazimin-A, and Niaziminin-B compounds from Moringa oleifera ethanolic leave extract were reported to have potent antihypertensive activity. Objective: These compounds were targeted with Angiotensin-converting enzyme [ACE] which is one of the main regulatory enzymes of the renin-angiotensin system. Methods: Protein-ligand docking of these compounds with [ACE] [both domain N and C] was conceded out through Autodock vina and visualization was done by chimera. Pharmacokinetics study of these compounds was predicted by ADME-Toxicity Prediction. Results: Niazicin-A, Niazimin-A, and Niaziminin-B showed high binding affinity with ACE and partially blocked the active sites of the enzyme. Niazicin-A, Niazimin-A and Niaziminin-B showed the estimated free binding energy of -7.6kcal/mol kcal/mol, -8.8kcal/mol and -8.0kcal/mol respectively with C-domain of ACE and -7.9kcal/mol, -8.5kcal/mol and -7.7kcal/mol respectively with N-domain of ACE. The compounds showed better binding energy with angiotensinconverting enzyme in comparison to Captopril -5.5kcal/mol and -5.6kcal/mol and Enalapril [standard] -8.4kcal/mol and -7.5kcal/mol with C and N domain, respectively. Conclusion: Computationally, the selected bioactive molecules have shown better binding energy to known standard drugs which have been already known for inhibition of ACE and can further act as a pharmacophore for in vitro and in vivo studies in the development of alternative medicine.


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