Synthesis of novel derivatives of oxindole, their urease inhibition and molecular docking studies

Taha, Muhammad; Ismail, Nor Hadiani; Khan, Ajmal; Shah, Syed Adnan Ali; Anwar, Ammarah; Halim, Sobia Ahsan; Fatmi, M. Qaiser; Imran, Syahrul; Rahim, Fazal; Khan, Khalid Mohammed

doi:10.1016/j.bmcl.2015.05.069

Cited by 82 publications

(31 citation statements)

References 39 publications

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“…However, the interaction with the active-site Ni 2+ was not found to be obvious. It was shown that 2-OCH 3 group affected the molecular conformation interacting with HPU, which enhanced the binding with ARG-338, a key residue reported previously as catalytic residue in the active site [32], resulting in lowered enzymatic activity. As far as JBU was concerned, 2-OCH 3 and 3-OCH 3 groups were observed to interact with ARG-639, a key residue located at the mobile flap covering the active site, hence preserving the flap in the open conformation and leading to urease inactivation.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

Zhou

Tan

et al. 2017

PLoS ONE

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In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/mL under neutral environment (pH 7.4), and from 75 to 100 μg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori urease (HPU) and jack bean urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known urease inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against urease inhibition than the competitive Ni2+ binding inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two ureases was reversible, further supporting that sulfhydryl group should be obligatory for urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective inhibitor of H. pylori and its urease targeting the sulfhydryl groups, representing a promising candidate as novel urease inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other urease-related diseases.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

Zhou

Tan

et al. 2017

PLoS ONE

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“…Indole‐2‐hydrazones were synthesized and evaluated for their antileishmanial activities . Oxindole derivatives were analyzed for their alpha‐glucosidase and urease inhibitory activities , and the molecular interactions of the active compounds within the urease enzyme binding sites were studied via molecular docking simulations.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, Solvatochromic Properties, and Antimicrobial‐radical Scavenging Activities of New Diazo Dyes Derived from Pyrazolo[1,5‐a]pyrimidine

Şener

Erişkin

Yavuz

et al. 2017

Journal of Heterocyclic Chem

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5‐Amino‐3‐methyl‐4‐phenylazo‐1H‐pyrazole and ethyl cyanoacetate reacted in solvent‐free media at 150°C to produce 7‐amino‐3‐phenylazo‐2‐methyl‐4H‐pyrazolo[1,5‐a]pyrimidine‐5‐one (3). A series of aromatic amines was coupled using this compound (3) and nitrous acid to produce new pyrazolo[1,5‐a] pyrimidine derivatives with two arylazo groups 4(a‐m). The structures of these dyes were determined via UV–vis, Fourier transform infrared, proton nuclear magnetic resonance, high‐resolution mass spectral data, and elemental analysis. After synthesis, the solvent and acid–base effects of the dyes were investigated within the UV–vis region. The antimicrobial properties of the dyes were also studied. All dyes exhibited activity against Gram‐positive and Gram‐negative bacteria, and even against fungi. The results were compared to conventional reference results from the antibiotics ciprofloxacin and ketoconazole. Antioxidant potentials were analyzed using in vitro antioxidant models on the basis of DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) radical scavenging activities. Most of the compounds exhibited excellent antioxidant activities. In particular, compound 4b had a higher activity than Vitamin C.

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“…bond distance amongst the H‐donor and the H‐acceptor atoms is less than 3.5 Å . The hydrogen bond distances of compounds ( 1‐1 a ) and ( 2‐2 a ) were less than 3.5 Å in respective 3OGN protein signifies strong hydrogen bonding.…”

Section: Resultsmentioning

confidence: 90%

Cu^II‐Tyrosinase Enzyme Catalyst‐Mediated Synthesis of 2‐Thioxopyrimidine Derivatives with Potential Mosquito Larvicidal Activity: Spectroscopic and Computational Investigation as well as Molecular Docking Interaction with OBPs of Culex quinquefasciatus

et al. 2020

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A series of 2-thioxo pyrimidine derivatives 1, (1 a-1 e) and 2, (2 a-2 e) were synthesized via Biginelli reaction by using Cu IItyrosinase (Cu II -Tyr) as an enzyme catalyst in up to 80-92% yield. The compounds 1, (1 a-1 e) and 2, (2 a-2 e) were characterized by IR, 1 H NMR, 13 C NMR, mass spectra and elemental analyses. The synthesized compounds 1, (1 a-1 e) and 2, (2 a-2 e) were screened for mosquito larvicidal activity against Culex quinquefasciatus. The compound 2 a was 80% mortality at 100 μg/mL with the LD 50 value of 55.94 μg/mL than the control Permethrin 60.03 μg/mL respectively. Molecular docking studies of synthesized compounds were carried out and the results proposed that the compound 2 a as a potential candidate to mosquito odorant-binding protein 3OGN inhibitors. In addition, computational studies, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies showed that the charge transfer occurs in the inside of the molecule and also gives the chemical reactivity descriptors, and molecular electrostatic potential (MESP) is also calculated. Therefore, experimental and theoretical studies were well supported for the compound 2 a as a potential larvicide activity aganist mosquito larvae of Culex quinquefasciatus.

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Synthesis of novel derivatives of oxindole, their urease inhibition and molecular docking studies

Cited by 82 publications

References 39 publications

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

Synthesis, Characterization, Solvatochromic Properties, and Antimicrobial‐radical Scavenging Activities of New Diazo Dyes Derived from Pyrazolo[1,5‐a]pyrimidine

Cu^II‐Tyrosinase Enzyme Catalyst‐Mediated Synthesis of 2‐Thioxopyrimidine Derivatives with Potential Mosquito Larvicidal Activity: Spectroscopic and Computational Investigation as well as Molecular Docking Interaction with OBPs of Culex quinquefasciatus

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Synthesis of novel derivatives of oxindole, their urease inhibition and molecular docking studies

Cited by 82 publications

References 39 publications

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism

Synthesis, Characterization, Solvatochromic Properties, and Antimicrobial‐radical Scavenging Activities of New Diazo Dyes Derived from Pyrazolo[1,5‐a]pyrimidine

CuII‐Tyrosinase Enzyme Catalyst‐Mediated Synthesis of 2‐Thioxopyrimidine Derivatives with Potential Mosquito Larvicidal Activity: Spectroscopic and Computational Investigation as well as Molecular Docking Interaction with OBPs of Culex quinquefasciatus

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Cu^II‐Tyrosinase Enzyme Catalyst‐Mediated Synthesis of 2‐Thioxopyrimidine Derivatives with Potential Mosquito Larvicidal Activity: Spectroscopic and Computational Investigation as well as Molecular Docking Interaction with OBPs of Culex quinquefasciatus