Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation

Peytam, Fariba; Adib, Mehdi; Mahernia, Shabnam; Rahmanian-Jazi, Mahmoud; Jahani, Mehdi; Masoudi, Behrad; Mahdavi, Mohammad; Amanlou, Massoud

doi:10.1016/j.bioorg.2019.02.051

Cited by 28 publications

(21 citation statements)

References 115 publications

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“…Other inhibitors that proved their urease inhibitory activity are compounds with isoindolin-1-one building blocks. 15 In addition to their vast range of pharmacologic effects, 21 they also demonstrated acceptable urease inhibition and interacted with the key residues and nickel ions in the active site. The isoindolin-1-one part also interacted with the key residues in the active site.…”

Section: Resultsmentioning

confidence: 99%

“…Yellow powder; yield: 70%; mp: 250 °C; 1 H NMR (500 MHz, DMSO-d 6 ) δ: 11.83 (s, 2H, 2 × NH Enol), 7.77 (d, J = 7.5 Hz, 1H, H 4 ), 7.64 (t, J = 7.5 Hz, 1H, H 2 ), 7.49 (t, J = 7.5 Hz, 1H, H 3 ), 7.42 (d, J = 7.8 Hz, 1H, H 1 ), 6.67 (s, 1H, H a Enol). 13 C NMR (125 MHz, DMSO-d 6 ) δ: 175.36, 170.66, 161.54, 149.52, 134.04, 128.85, 127.26, 125.02, 122.86, 100.92, 94.24, 74.86; MS ( m/z , %): 276.1 (M + , 24), 247.1, 15 231.1, 22 133.1 (100), 105.1, 17 77.1; 17 Tautomeric form (%): 100 Enol.…”

Section: Methodsmentioning

confidence: 99%

“… 14 Furthermore, urease inhibitory activity of different isoindolin-1-one derivatives was also reported. 15 Therefore, in this article, based on the mentioned studies and our computer-aided calculations, novel isoindolin-1-one derivatives that are fused to different barbiturates were designed and synthesized. Then, the urease inhibitory activity of the synthesized compounds was evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Isoindolin-1-ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation

et al. 2022

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Helicobacter pylori -induced ulcers and gastric cancer have been one of the main obstacles that the human community has ever struggled with, especially in recent decades. Several different attempts have been made to eradicate this group. One of the most widely used attempts is to inhibit the critical enzyme that facilitates its survival, the urease enzyme. Therefore, in this study, isoindolin-1-ones fused to barbiturates were designed, synthesized, and evaluated for their in vitro urease inhibitory activity as novel inhibitors for the urease enzyme. The synthesis route consisted of two steps. These steps increased the yield rate and decreased the percentage of byproducts while approaching green chemistry using ethanol and water as green solvents and microwave irradiation instead of conventional methods. In vitro urease inhibitory results indicated that all the compounds had higher inhibitory activity than the standard inhibitor, thiourea, and compound 5b proved to be the most potent inhibitor (IC 50 = 0.82 ± 0.03 μM). A molecular docking study was performed to understand the interaction between compounds 5a–n and Jack bean urease enzyme. The results of the molecular docking study were also in harmony with the in vitro results, which are discussed in detail later in this study.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Isoindolin-1-ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation

et al. 2022

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“…During current years, several structural classes of urease inhibitors have been reported including hydroxamic acids, phosphoramidates, urea and thiourea derivatives, oxoindoline and isoindolin‐1‐one derivatives, polyphenols, isoniazids, thiosemicarbazones, benzimidazoles, benzophenone sulfonamides, catechol‐based inhibitors, diflunisal derivatives, aryl urea‐triazole‐based derivatives, 1,3,4‐oxadiazoles, cinnamate‐based phosphonic acids, coumarin‐hybrids, and metal complexes …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4‐Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate

Ashani

Azizian

Alavijeh

et al. 2020

Chemistry & Biodiversity

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A series of new deferasirox derivatives were synthesized through the reaction of monosubstituted hydrazides with 2-(2-hydroxyphenyl)-4H-benzo[e] [1,3]oxazin-4-one. For the first time, deferasirox and some of its derivatives were evaluated for their in vitro inhibitory activity against Jack bean urease. The potencies of the members of this class of compounds are higher than that of acetohydroxamic acid. Two compounds, bearing tetrazole and hydrazine derivatives (bioisoester of carboxylate group), represented the most potent urease inhibitory activity with IC 50 values of 1.268 and 3.254 μM, respectively. In silico docking studies were performed to delineate possible binding modes of the compounds with the enzyme, urease. Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its crucial amino acid residues, CME592 and His593. The overall results of urease inhibition have shown that these target compounds can be further optimized and developed as a lead skeleton for the discovery of novel urease inhibitors Figure 1. The structure of DFX and its complexation with iron.Scheme 5. The proposed reaction mechanism for the synthesis of DFX and its analogs 7a -7e. two ionic bonds with two Ni 2 + ions. Also, the binding mode of DFX was depicted in Figure 4b, which revealed that like AHA carboxylate group pointed to the bi-nickel ion center. Besides, DFX formed a π -π Figure 2. The location of JBU active site over C-terminal (αβ) 8 TIM barrel domain (a), close-up representation of the active site, the AHA co-crystallized, and the corresponding re-docked form are represented in green and cyan color, respectively (b).Figure 3. Representation of two different docking poses of compounds relative to bi-nickel center over JBU active site: Compounds with 1,2,4-triazole-N 1 -substituted oriented toward the metal center (a), and compounds with 2-hydroxyphenyl pointed one (b). 3,5bis(2-hydroxyphenyl) moiety, related N 1 -substitution and 1,2,4-triazole ring are shown in red, yellow, and navy, respectively.

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“…Norcantharimide derivatives are known to be potential anticancer agents and also have positively effect on inflammatory pathologies including cancer . Isoindole‐1,3‐dione derivatives have crucial medicinal features such as analgesic, antifungal, antibacterial, anti‐microbial, anti‐tumor, besides their capability to inhibit acetylcholinesterase (AChE) and cyclooxygenase (COX) …”

Section: Introductionmentioning

confidence: 99%

New Isoindole‐1,3‐dione Substituted Sulfonamides as Potent Inhibitors of Carbonic Anhydrase and Acetylcholinesterase: Design, Synthesis, and Biological Evaluation

et al. 2019

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Herein, a series of isoindole‐1,3‐dione substituted sulfonamide derivatives (3, 4 a–k) were designed, synthesized, and biologically evaluated, as inhibitors of carbonic anhydrase (CA) and acetylcholinesterase (AChE). CA and AChE inhibitory activities of newly synthesized isoindole‐1,3‐dione substituted sulfonamides compounds (3, 4 a–k) towards the hCA I, II, and AChE were evaluated utilizing the Verpoorte's and Ellman's assays and checked against that of standard inhibitors, acetazolamide (AAZ) and tacrine (TAC). The developed compounds (3, 4 a–k) showed the potent hCA isoenzyme inhibitory effect with Ki constants ranging from 7.96 to 48.34 nM, compared to AAZ (Kis; 436.20 nM for hCA I and 93.53 nM for hCA II). Among these derivatives; 1,3‐dioxo‐1,3‐dihydroisobenzofuran‐5‐carbocyclic acid (3) and benzyl‐1,3‐dioxo‐2‐(4‐sulfomophenyl)isoindoline‐5‐carboxylate (4 i) determined to be effective AChE inhibitors (Kis, 103.51 and 108.92 nM, respectively); these compounds were almost as potent to TAC (Ki, 109.75 nM). Furthermore, molecular docking studies of derivatives 3 and 4 i were carried out utilizing the crystal structures of hCA I (PDB Code: 4WR7), II (PDB Code: 4HT0) isozymes and AChE (PDB Code: 4EY7) receptors to study their binding interactions.

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Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation

Cited by 28 publications

References 115 publications

Isoindolin-1-ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation

Isoindolin-1-ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation

Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4‐Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate

New Isoindole‐1,3‐dione Substituted Sulfonamides as Potent Inhibitors of Carbonic Anhydrase and Acetylcholinesterase: Design, Synthesis, and Biological Evaluation

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