Synthesis, crystal structure and biological evaluation of new phosphoramide derivatives as urease inhibitors using docking, QSAR and kinetic studies

Gholivand, Khodayar; Pooyan, Mahsa; Mohammadpanah, Fahimeh; Pirastefar, Foroogh; Junk, ‬Peter C.; Wang, Jun; Valmoozi, Ali Asghar Ebrahimi; Mani-Varnosfaderani, Ahmad

doi:10.1016/j.bioorg.2019.01.064

Cited by 21 publications

(9 citation statements)

References 41 publications

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“…Different functional groups, topological, geometrical and constitutional descriptors for each molecule were calculated by Dragon software. Gaussian 03 was also employed for calculation of different quantum chemical descriptors including, energies of highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), the energy difference between LUMO and HOMO (ΔE L−H ), dipole moment (DM), charges on atoms (Qi) and total energy (E), electrophilicity (ω), molecular volume (Mv), polarizability (PL, the charge difference between the atoms in functional groups), electronic chemical potential (μ), chemical hardness (η), Chemical softness (S), and chemical power (Cπ) [ 35 , 56 ].…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, we have recently reporteed some of these compounds with both abilities to inhibits the acetylcholinesterase enzyme and low human toxicity. [31] , [32] , [33] Among the various phosphoramide derivatives [ 31 , [33] , [34] , [35] ], we have studied phosphoguanidines and phosphopyrazines as effective compounds in drug design because of their extensive biological properties [ 31 , 33 ]. Due to the fact that Phosphoramides are able to inhibit the main protease [36] , In this work we selected 35 phosphoramide compounds including the guanidine and pyrazine with the general formula (R 1 )(R 2 )P(X)–Y, that X=O or S, Y= creatine, amino pyrazine, amino benzimidazole, or amino pyrimidines, R 1 =(C 6 H 5 , OC 6 H 5 , OCH 3 , or OCH 2 CH 3 ), and R 2 =(R, Y) ( Figure 1 , Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

Gholivand

Mohammadpanah

Pooyan

et al. 2022

Journal of Molecular Structure

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The recent prevalence of coronavirus disease in 2019 (COVID-19) has triggered widespread global health concerns.Antiviral drugs based on phosphoramides have significant inhibitory activity against the main protease (M pro ) of the virus and prevent transcription and viral replication. Hence, in order to design and introduce a group of inhibitors affecting the coronavirus, 35 phosphoramide compounds based on phospho-guanine and phospho-pyrazine derivatives were selected for molecular docking study. The results showed that most phosphoguanides containing the amino benzimidazole have a high interaction tendency with COVID-19. Among them, compound 19 was identified as the strongest inhibitor with the -9.570 kcal/mol binding energy whereas, the binding energy of Remdesivir is -6.75 kcal/mol. The quantitative structure-activity relationship (QSAR) results demonstrated that the number of aromatic rings, amide's nitrogens and their ability in π-staking, and hydrogen interactions with M pro active sites are major factors contributing to the inhibitory activity of these compounds.Also, the NCI-RDG and DFT results were in good accordance with those of QSAR and molecular docking. The findings of this investigation can be underlying the synthesis of effective and efficient drugs against COVID-19.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

Gholivand

Mohammadpanah

Pooyan

et al. 2022

Journal of Molecular Structure

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“…34,38 It has been discovered that certain urease inhibitors suppressed the activity of JBU by the interaction with the thiol of residues, particularly Cys592. 38,45 As indicated by our results, NC could interact with the lateral chains of the above-mentioned residues, particularly Cys592 on the flap of the active site, thus keeping the flap in an open state, leading to urease inactivation. Consistent with the conclusions drawn from the urease protective assays of active site binding inhibitors, the results of molecular docking further confirmed that the thiol of the active site cysteine was involved in NC inhibition of urease.…”

Section: Discussionmentioning

confidence: 54%

“…Apart from the structures directly participating in the active site, other key amino acid residues around the active site also played an important role in urease catalysis . In the course of urease catalyzing normal urea, the flexible flap could efficiently activate inert urea and promote enzyme activation through an open-close-open process. , Cys592 variation restricted the mobility of the flap, resulting in reaction disorder and decreased urease vitality. − Furthermore, additional amino acid residues of the flap at the inlet of the binding pocket, including Arg439, Ala440, and Ala636, take part in the substrate binding, stabilize the catalytic transient state, and boost the reaction by H-bonds. , It has been discovered that certain urease inhibitors suppressed the activity of JBU by the interaction with the thiol of residues, particularly Cys592. , …”

Section: Discussionmentioning

confidence: 99%

Inactivation of Jack Bean Urease by Nitidine Chloride from Zanthoxylum nitidum: Elucidation of Inhibitory Efficacy, Kinetics and Mechanism

Lü

Tan

et al. 2021

J. Agric. Food Chem.

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Urease is a metalloenzyme that catalyzes the hydrolysis of urea into ammonia and carbon dioxide, which has a negative impact on human health and agriculture. In this study, the inactivation of jack bean urease by nitidine chloride (NC) was investigated to elucidate the inhibitory effect, kinetics, and underlying mechanism of action. The results showed that NC acted as a concentration- and time-dependent inhibitor with an IC50 value of 33.2 ± 4.8 μM and exhibited a similar inhibitory effect to acetohydroxamic acid (IC50 = 31.7 ± 5.8 μM). Further kinetic analysis demonstrated that NC was a slow-binding and non-competitive inhibitor for urease. Thiol-blocking reagents (dithiothreitol, glutathione, and l-cysteine) significantly retarded urease inactivation, while Ni2+ competitive inhibitors (boric acid and sodium fluoride) synergetically suppressed urease with NC, suggesting that the active site sulfhydryl groups were possibly obligatory for NC blocking urease. Molecular docking simulation further argued its inhibition mechanism. Additionally, NC-induced deactivation of urease was verified to be reversible since the inactivated enzyme could be reactivated by glutathione. Taking together, NC was a non-competitive inhibitor targeting the thiol group at the active site of urease with characteristics of concentration dependence, reversibility, and slow binding, serving as a promising novel urease suppressant.

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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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Synthesis, crystal structure and biological evaluation of new phosphoramide derivatives as urease inhibitors using docking, QSAR and kinetic studies

Cited by 21 publications

References 41 publications

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

Inactivation of Jack Bean Urease by Nitidine Chloride from Zanthoxylum nitidum: Elucidation of Inhibitory Efficacy, Kinetics and Mechanism

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

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