Binding mode prediction and identification of new lead compounds from natural products as renin and angiotensin converting enzyme inhibitors

Moorthy, N. S. Hari Narayana; Brás, Natércia F.; Ramos, María J.; Fernandes, Pedro A.

doi:10.1039/c4ra00856a

Cited by 7 publications

(2 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They reported the mode of action of acteoside and osmanthuside β6 as ACE inhibitors. Finally, Moorthy et al [70] performed virtual screening studies with docking and pharmacophore methods on a natural products data set to investigate its inhibitory effect on cardiovascular targets such as renin (REN) and ACE. They identified the compound Nat-59 that has remarkable interaction with both the studied targets (ACE and REN).…”

Section: -Bis(dihydrocaffeoyl)-spermidine)mentioning

confidence: 99%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

View full text Add to dashboard Cite

The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. In this sense, ACE inhibitors are bioactive substances with potential use as medicinal products for treatment or prevention of hypertension, heart failures, myocardial infarction, and other important diseases. This review examined the most recent literature reporting ACE inhibitors with the help of molecular modeling. The examples exposed here demonstrate that molecular modeling methods, including docking, molecular dynamics (MD) simulations, quantitative structure-activity relationship (QSAR), etc, are essential for a complete structural picture of the mode of action of ACE inhibitors, where molecular docking has a key role. Examples show that too many works identified ACE inhibitory activities of natural peptides and peptides obtained from hydrolysates. In addition, other works report non-peptide compounds extracted from natural sources and synthetic compounds. In all these cases, molecular docking was used to provide explanation of the chemical interactions between inhibitors and the ACE binding sites. For docking applications, most of the examples exposed here do not consider that: (i) ACE has two domains (nACE and cACE) with available X-ray structures, which are relevant for the design of selective inhibitors, and (ii) nACE and cACE binding sites have large dimensions, which leads to non-reliable solutions during docking calculations. In support of the solution of these problems, the structural information found in Protein Data Bank (PDB) was used to perform an interaction fingerprints (IFPs) analysis applied on both nACE and cACE domains. This analysis provides plots that identify the chemical interactions between ligands and both ACE binding sites, which can be used to guide docking experiments in the search of selective natural components or novel drugs. In addition, the use of hydrogen bond constraints in the S2 and S2′ subsites of nACE and cACE are suggested to guarantee that docking solutions are reliable.

show abstract

Section: -Bis(dihydrocaffeoyl)-spermidine)mentioning

confidence: 99%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

View full text Add to dashboard Cite

show abstract

“…35 During the simulations, periodic boundary conditions were employed and all electrostatic interactions were calculated using the particle-mesh Ewald (PME) method with a dielectric constant of unity. 37,38 A 10.0 Å cutoff was used to calculate the direct space sum of PME. The SHAKE algorithm was used to restrain bond lengths involving hydrogen atoms.…”

Section: Molecular Dynamic Simulationsmentioning

confidence: 99%

Structural insights into flavones as protein kinase CK2 inhibitors derived from a combined computational study

Tian

et al. 2015

RSC Adv.

View full text Add to dashboard Cite

show abstract

An Integrated Approach for Fragment‐Based Lead Discovery: Virtual, NMR, and High‐Throughput Screening Combined with Structure‐Guided Design. Application to the Aspartyl Protease Renin.

Rüdisser

Vangrevelinghe

Maibaum

2016

Methods and Principles in Medicinal Chemistry

View full text Add to dashboard Cite

Binding mode prediction and identification of new lead compounds from natural products as renin and angiotensin converting enzyme inhibitors

Abstract: In this study a novel renin and ACE inhibitor was developed from natural products using computational techniques. Molecular dynamic simulations showed that the new lead compound has significant binding to the targets.

Cited by 7 publications

References 47 publications

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Structural insights into flavones as protein kinase CK2 inhibitors derived from a combined computational study

An Integrated Approach for Fragment‐Based Lead Discovery: Virtual, NMR, and High‐Throughput Screening Combined with Structure‐Guided Design. Application to the Aspartyl Protease Renin.

Contact Info

Product

Resources

About