Potential Angiotensin Converting Enzyme Inhibitors from Moringa oleifera

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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POTENSI SENYAWA BIOAKTIF TANAMAN KELOR PENGHAMBAT INTERAKSI ANGIOTENSIN-CONVERTING ENZYME 2 PADA SINDROMA SARS-COV-2

Jurnal Bioteknologi & Biosains Indonesia (JBBI) ◽

10.29122/jbbi.v7i2.4156 ◽

2020 ◽

Vol 7 (2) ◽

pp. 259-270

Author(s):

Maharani Pertiwi Koentjoro ◽

Adyan Donastin ◽

Endry Nugroho Prasetyo

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Protein Data Bank ◽

Active Sites ◽

Moringa Oleifera ◽

Data Bank ◽

Converting Enzyme ◽

Ligand Complex ◽

Angiotensin Converting Enzyme 2 ◽

Pubchem Database

The Potential of Moringa oleifera Bioactive Compounds for Inhibiting Angiotensin-Converting Enzyme 2 Interaction in SARS-Cov-2 Syndrome Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) is a threat to human health. This infection is determined by the interaction of the spike S1 domain protein with angiotensin-converting enzyme 2 (ACE2) in the epithelial cells of the respiratory tract, especially the lungs. ACE2 inhibition is an important target in controlling COVID-19. Flavonoids of medicinal plants, are known to interfere with ACE (ACE2 homologous). Therefore, this study aims to explore the ability of apiin, epicatechin, and hesperetin from Moringa oleifera in interacting with the ACE2 using MOE 2008.10. The ligand molecules were prepared from PubChem database. The ACE2 protein was retrieved from Protein Data Bank (ID 1R4L) and analyzed for the active sites. Analysis of docking scores and hydrogen bonds of ACE2-ligand complex and active site showed that the affinity of flavonoids can be ranked as hesperetin > epicatechin > apiin > C19H23Cl2N3O4. The results provided computational information that apiin, epicatechin, and hesperetin have the potential to prevent COVID-19 infection. The prediction of activity spectra for substances (PASS) score showed the ligand displays antiviral activity. Infeksi severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pada pandemi coronavirus disease 2019 (COVID-19) menjadi ancaman dunia kesehatan saat ini. Infeksi SARS-CoV-2 ditentukan oleh interaksi protein spike envelope S1 domain dengan reseptor angiotensin-converting enzyme 2 (ACE2) yang diekspresikan pada sel epitel saluran pernafasan terutama paru-paru. Mekanisme penghambatan ACE2 menjadi target penting dalam pengendalian COVID-19. Senyawa bioaktif tanaman obat, seperti flavonoid diketahui mampu mengganggu fungsi banyak makromolekul termasuk ACE (homolog dengan ACE2). Penelitian ini bertujuan mengeksplorasi kemampuan senyawa apiin, epicatechin, dan hesperetin dari Moringa oleifera dalam berinteraksi dengan sisi aktif ACE2 menggunakan metode penambatan molekul. Studi dilakukan dengan preparasi struktur molekul ligan dari PubChem database dan diolah dengan MOE 2008.10. Selanjutnya, data protein ACE2 (Protein Data Bank ID 1R4L) dianalisis sisi aktifnya untuk mengetahui lokasi penambatan ligan senyawa. Analisis skor docking dan ikatan hydrogen komplek ligan dan sisi aktif ACE2 menunjukkan bahwa afinitas flavonoid dapat diperingkatkan sebagai afinitas hesperetin > epicatechin > apiin > C19H23Cl2N3O4. Ketiga ligan senyawa yang terkandung dalam M. oleifera secara in silico mampu mengikat sisi aktif ACE2, sehingga berpotensi mencegah infeksi COVID-19. Skor PASS (prediction of activity spectra for substances) menunjukkan aktivitas biologis ligan yang menyerupai antiviral.

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

Food & Function ◽

10.1039/d1fo01798e ◽

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...

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Central and Peripheral Inhibition of Angiotensin Converting Enzyme (ACE) in the Shr: Correlation with the Antihypertensive Activity of ACE Inhibitors

Clinical and Experimental Hypertension Part A Theory and Practice ◽

10.3109/10641968709164213 ◽

1987 ◽

Vol 9 (2-3) ◽

pp. 461-468 ◽

Cited By ~ 9

Author(s):

Jon A. Norman ◽

Monique Lehmann ◽

Frank R. Goodman ◽

Bryce W. Barclay ◽

Mark B. Zimmerman

Keyword(s):

Angiotensin Converting Enzyme ◽

Ace Inhibitors ◽

Antihypertensive Activity ◽

Converting Enzyme ◽

Peripheral Inhibition

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Experimental and clinical antihypertensive activity of Matricaria chamomilla extracts and their angiotensin-converting enzyme inhibitory activity

Phytotherapy Research ◽

10.1002/ptr.6086 ◽

2018 ◽

Vol 32 (8) ◽

pp. 1564-1573 ◽

Cited By ~ 2

Author(s):

Amani A. Awaad ◽

Reham M. El-Meligy ◽

Ghada M. Zain ◽

Amal A. Safhi ◽

Noura A. AL Qurain ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Inhibitory Activity ◽

Antihypertensive Activity ◽

Converting Enzyme ◽

Matricaria Chamomilla

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

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i2.29106 ◽

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.

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