scholarly journals VIRTUAL SCREENING OF HETEROCYCLIC COMPOUNDS AGAINST ANGIOTENSIN-CONVERTING ENZYME FOR POTENTIAL ANTIHYPERTENSIVE INHIBITORS

2019 ◽  
pp. 350-355
Author(s):  
ZOZIMUS DIVYA LOBO C ◽  
SYED MOHAMED A ◽  
GNANENDRA SHANMUGAM
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Heterocyclic Compounds ◽  
Density Functional ◽  
Energy Gap ◽  
3D Structure ◽  
Antihypertensive Activity ◽  
Converting Enzyme ◽  
Molecular Electronic ◽  
3D Structures

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.

scholarly journals A clinical dose of angiotensin-converting enzyme (ACE) inhibitor and heterozygous ACE deletion exacerbate Alzheimer's disease pathology in mice

2019 ◽  
Vol 294 (25) ◽  
pp. 9760-9770 ◽  
Author(s):  
Shuyu Liu ◽  
Fujiko Ando ◽  
Yu Fujita ◽  
Junjun Liu ◽  
Tomoji Maeda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Precursor Protein ◽  
Causative Role ◽  
Converting Enzyme ◽  
Clinical Dose

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic β-amyloid protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage. Whether ACE inhibition enhances Aβ42 aggregation or impairs human cognitive ability are very important issues for preventing AD onset and for optimal hypertension management. In an 8-year longitudinal study, we found here that the mean intelligence quotient of male, but not female, hypertensive patients taking ACE inhibitors declined more rapidly than that of others taking no ACE inhibitors. Moreover, the sera of all AD patients exhibited a decrease in Aβ42-to-Aβ40–converting activity compared with sera from age-matched healthy individuals. Using human amyloid precursor protein transgenic mice, we found that a clinical dose of an ACE inhibitor was sufficient to increase brain amyloid deposition. We also generated human amyloid precursor protein/ACE+/− mice and found that a decrease in ACE levels promoted Aβ42 deposition and increased the number of apoptotic neurons. These results suggest that inhibition of ACE activity is a risk factor for impaired human cognition and for triggering AD onset.

Kefir peptide (Kef-1) as an emerging approach for the treatment of oxidative stress and inflammation in 2K1C mice

2022 ◽  
Author(s):  
Rafaela Aires ◽  
Fernanda Gobbi Amorim ◽  
Larissa Zambom Côco ◽  
Amanda Pompermayer da Conceição ◽  
Tadeu Ériton Caliman Zanardo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Converting Enzyme ◽  
Ace Inhibitors ◽  
Bioactive Molecules ◽  
Converting Enzyme ◽  
The Rich ◽  
Potential Use

The benefits of Kefir consumption are due, in part, to the rich composition of bioactive molecules released from fermentation. Angiotensin-converting enzyme (ACE) inhibitors are bioactive molecules with potential use in...

Sequence analysis, structure prediction of receptor proteins and In silico study of potential inhibitors for management of life threatening COVID-19

2021 ◽  
Vol 18 ◽  
Author(s):  
Hriday K. Basak ◽  
Soumen Saha ◽  
Joydeep Ghosh ◽  
Uttam Paswan ◽  
Sujoy Karmakar ◽  
...  
Keyword(s):  
Binding Site ◽  
Ursolic Acid ◽  
Density Functional ◽  
Actinomycin D ◽  
3D Structure ◽  
Natural Compounds ◽  
Surface Glycoprotein ◽  
Basis Set ◽  
3D Structures ◽  
Potential Inhibitors

Background: Treatment of the Covid-19 pandemic caused by the highly contagious and pathogenic SARS-CoV-2 is a global menace. Day by day this pandemic is getting worse. Doctors, Scientists and Researchers across the world are urgently scrambling for a cure for novel corona virus and continuously working at break neck speed to develop vaccine or drugs. But to date, there are no specific drugs or vaccine available in the market to cope up the virus. Objective: The present study helps us to elucidate 3D structures of SARS-CoV-2 proteins and also to identify best natural compounds as potential inhibitors against COVID-19. Methods: The 3D structures of the proteins were constructed using Modeller 9.16 modeling tool. Modelled proteins were validated with PROCHECK by Ramachandran plot analysis. In this study a small library of natural compounds (fifty compounds) was docked to the ACE2 binding site of the modelled surface glycoprotein of SARS-CoV-2 using Auto Dock Vina to repurpose these inhibitors for SARS-CoV-2. Conceptual density functional theory calculations of best eight compounds had been performed by Gaussian-09. Geometry optimizations for these molecules were done at M06-2X/ def2-TZVP level of theory. ADME parameters, pharmacokinetic properties and drug likeliness of the compounds were analyzed in the swissADME website. Results: In this study we analysed the sequences of surface glycoprotein, nucleocapsid phosphoprotein and envelope protein obtained from different parts of the globe. We have modelled all the different sequences of surface glycoprotein and envelop protein in order to derive 3D structure of a molecular target which is essential for the development of therapeutics. Different electronic properties of the inhibitors have been calculated using DFT through M06-2X functional with def2-TZVP basis set. Docking result at the hACE2 binding site of all modelled surface glycoproteins of SARS-CoV-2 showed that all the eight inhibitors (Actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) studied here many folds better compared to hydroxychloroquine which has been found to be effective to treat patients suffering fromCOVID-19 pandemic. All the inhibitors meet most of criteria of drug likeness assessment. Conclusion: We will expect that eight compounds (Actinomycin D, avellanin C, ichangin, kanglemycin A, obacunone, ursolic acid, ansamiotocin P-3 and isomitomycin A) can be used as potential inhibitors against SARS-CoV-2.

scholarly journals Normal-phase thin-layer chromatography of some angiotensin converting enzyme (ACE) inhibitors and their metabolites

2009 ◽  
Vol 74 (6) ◽  
pp. 677-688 ◽  
Author(s):  
Jadranka Odovic ◽  
Mirjana Aleksic ◽  
Biljana Stojimirovic ◽  
Dusanka Milojkovic-Opsenica ◽  
Zivoslav Tesic
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Ace Inhibitors ◽  
Reversed Phase ◽  
Normal Phase ◽  
Converting Enzyme ◽  
Reversed Phase Chromatography ◽  
Aqueous Solvent ◽  
Layer Chromatography

The separation and chromatographic behaviour of five ACE (angiotensin converting enzyme) inhibitors and their four active metabolites were investigated by normal-phase thin-layer chromatography on silica using several mono- and binary non-aqueous solvent systems. The linear relationship between the RM values and the composition of employed mobile phase was obtained. The hydrophobicity parameters 0M R and C0 were determined from the regression data of the plots, analogous to reversed-phase chromatography. The chromatographically obtained hydrophobicity parameters were correlated with the calculated log P values. The current results were correlated with the lipophilicity of the studied ACE inhibitors and their metabolites, previously estimated by reversed-phase chromatography.

scholarly journals The effect of angiotensin-converting enzyme inhibitors on clinical outcomes in patients with ischemic cardiomyopathy and midrange ejection fraction: a post hoc subgroup analysis from the PEACE trial

2018 ◽  
Vol 12 (12) ◽  
pp. 351-359 ◽  
Author(s):  
Talal Alzahrani ◽  
John Tiu ◽  
Gurusher Panjrath ◽  
Allen Solomon
Keyword(s):  
Ejection Fraction ◽  
Angiotensin Converting Enzyme ◽  
Clinical Outcomes ◽  
Ace Inhibitors ◽  
Subgroup Analysis ◽  
Ischemic Cardiomyopathy ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
All Cause Mortality ◽  
Post Hoc

Background: There have been significant advances in the treatment of patients with cardiomyopathy with reduced ejection fraction (EF < 40%). However, there is a dearth of information in the treatment of patients with cardiomyopathy and midrange EF (40–50%). Current guidelines state to treat these patients similarly to patients with cardiomyopathy and preserved EF. Data from the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial were used to elucidate whether angiotensin-converting enzyme (ACE) inhibitors improve clinical outcomes in patients with ischemic cardiomyopathy and midrange EF. Methods: A post hoc subgroup analysis of the PEACE trial was conducted to evaluate the effect of ACE inhibitors in a subgroup of patients with ischemic cardiomyopathy and midrange EF (40–50%). A Chi-square test and a Student‘s t-test were used to examine and compare the binary and continuous variables of baseline characteristics and outcomes between experimental and comparison groups. Results: We studied a subgroup of patients from the PEACE trial with ischemic cardiomyopathy and midrange EF ( n = 2512 of 8290 total patients). Patients were assigned to either the interventional group ( n = 1247) or the placebo group ( n = 1265). There were no significant differences in baseline demographic and health characteristics between the two groups. During a total of 7 years (mean 4.7 years) of follow up, the risk of composite outcomes [all-cause mortality, nonfatal myocardial infarction, and stroke; relative risk (RR) 0.79, 95% confidence interval (CI) 0.63–0.98; p = 0.03] and all-cause mortality (RR 0.85, 95% CI 0.73–0.99; p = 0.03) was reduced in patients treated with trandolapril. Conclusion: This study revealed the benefit of ACE inhibitors among patients with ischemic cardiomyopathy and midrange EF.

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