Design, synthesis and biological evaluation of Schiff bases of 4-amino-1,2,4-triazole derivatives as potent angiotensin converting enzyme inhibitors and antioxidant activities

Saadaoui, Ikram; Krichen, Fatma; Salah, Bochra Ben; Mansour, Riadh Ben; Miled, Nabil; Bougatef, Ali; Kossentini, Mohamed

doi:10.1016/j.molstruc.2018.12.008

Cited by 51 publications

(17 citation statements)

References 44 publications

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“…Other examples show studies on the discovery of novel synthetic ACE inhibitors with the help of molecular modeling methods [71][72][73][74]. For instance, Saadaoui et al [72] synthesized Schiff bases of 4-amino-1,2,4-triazole derivatives and evaluated them as ACE inhibitors. They observed that the synthetic compounds displayed virtually no cytotoxicity and they proposed the mode of action of the compounds by using in silico molecular docking.…”

Section: -Bis(dihydrocaffeoyl)-spermidine)mentioning

confidence: 99%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

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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.

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Section: -Bis(dihydrocaffeoyl)-spermidine)mentioning

confidence: 99%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

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“…Schiff bases containing a heterocyclic 1,2,4-triazole moiety have been investigated for their bioactivities and pharmaceutical applications (Bhalgat et al, 2014;Saadaoui et al, 2019;Zhang et al, 2019;Akin et al, 2019). Recently, the structures of Schiff bases obtained from 3-amino-1H-1,2,4-triazole have been reported in detail (Kołodziej et al, 2019).…”

Section: Structure Descriptionmentioning

confidence: 99%

N-[(E)-Quinolin-2-ylmethylidene]-1,2,4-triazol-4-amine hemihydrate

et al. 2020

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The title hemihydrate, C12H9N5·0.5H2O, was isolated from the condensation reaction of quinoline-2-carbaldehyde with 4-amino-4H-1,2,4-triazole. The Schiff base molecule adopts an E configuration about the C=N bond and is approximately planar, with a dihedral angle between the quinoline ring system and the 1,2,4-triazole ring of 12.2 (1)°. In the crystal, one water molecule bridges two Schiff base molecules via O—H...N hydrogen bonds. The Schiff base molecules are interconnected by π–π stacking interactions [centroid-centroid distances of 3.7486 (7) and 3.9003 (7) Å] into columns along [1\overline{1}0].

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“…Based on the last 40 years of academic and pharmaceutical industry inventions, only bedaquiline was the first novel anti-TB drug permitted by the United States Food and Drug Administration (US FDA) authority in December 2012, for the treatment of MDR-TB, [6] while delamanid was the second anti-TB agent to be approved by the European Medicines Agency in late 2013 [7] and pretomanid was the third drug to be approved by the US FDA in August 2019 [8,9] (Figure 1). Triazole pharmacophore with various functional groups/substitutions has been reported for its promising anti-TB [10][11][12][13][14][15][16][17][18][19][20][21], antiviral [22], antibacterial [23,24], antifungal [25,26], antioxidant [27][28][29][30], and antiglycation properties [31]. In addition, it also serves as an opener of Ca( 2+ )-activated potassium (maxi-K) channels [32] and demonstrates molluscicidal [33], hypoglycemic [34], antihypertensive and blood platelet aggregation inhibition [35] activities.…”

Section: Introductionmentioning

confidence: 99%

“…Triazole pharmacophore with various functional groups/substitutions has been reported for its promising anti-TB [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], antiviral [ 22 ], antibacterial [ 23 , 24 ], antifungal [ 25 , 26 ], antioxidant [ 27 , 28 , 29 , 30 ], and antiglycation properties [ 31 ]. In addition, it also serves as an opener of Ca( 2+ )-activated potassium (maxi-K) channels [ 32 ] and demonstrates molluscicidal [ 33 ], hypoglycemic [ 34 ], antihypertensive and blood platelet aggregation inhibition [ 35 ] activities.…”

Section: Introductionmentioning

confidence: 99%

Anti-Tubercular Properties of 4-Amino-5-(4-Fluoro-3- Phenoxyphenyl)-4H-1,2,4-Triazole-3-Thiol and Its Schiff Bases: Computational Input and Molecular Dynamics

et al. 2020

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In the present investigation, the parent compound 4-amino-5-(4-fluoro-3-phenoxyphenyl)-4H-1,2,4-triazole-3-thiol (1) and its Schiff bases 2, 3, and 4 were subjected to whole-cell anti-TB against H37Rv and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) by resazurin microtiter assay (REMA) plate method. Test compound 1 exhibited promising anti-TB activity against H37Rv and MDR strains of MTB at 5.5 µg/mL and 11 µg/mL, respectively. An attempt to identify the suitable molecular target for compound 1 was performed using a set of triazole thiol cellular targets, including β-ketoacyl carrier protein synthase III (FABH), β-ketoacyl ACP synthase I (KasA), CYP121, dihydrofolate reductase, enoyl-acyl carrier protein reductase, and N-acetylglucosamine-1-phosphate uridyltransferase. MTB β-ketoacyl ACP synthase I (KasA) was identified as the cellular target for the promising anti-TB parent compound 1 via docking and molecular dynamics simulation. MM(GB/PB)SA binding free energy calculation revealed stronger binding of compound 1 compared with KasA standard inhibitor thiolactomycin (TLM). The inhibitory mechanism of test compound 1 involves the formation of hydrogen bonding with the catalytic histidine residues, and it also impedes access of fatty-acid substrates to the active site through interference with α5–α6 helix movement. Test compound 1-specific structural changes at the ALA274–ALA281 loop might be the contributing factor underlying the stronger anti-TB effect of compound 1 when compared with TLM, as it tends to adopt a closed conformation for the access of malonyl substrate to its binding site.

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Design, synthesis and biological evaluation of Schiff bases of 4-amino-1,2,4-triazole derivatives as potent angiotensin converting enzyme inhibitors and antioxidant activities

Cited by 51 publications

References 44 publications

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

N-[(E)-Quinolin-2-ylmethylidene]-1,2,4-triazol-4-amine hemihydrate

Anti-Tubercular Properties of 4-Amino-5-(4-Fluoro-3- Phenoxyphenyl)-4H-1,2,4-Triazole-3-Thiol and Its Schiff Bases: Computational Input and Molecular Dynamics

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