Synthesis, urease inhibition screening and molecular docking studies of piperonal based imine derivatives

Abid, Obaid‐ur‐Rahman; Daud, Saima; Sardar, Asma; Rehman, Wajid; Wadood, Abdul; Rehman, Ashfaq Ur; Akhter, Toheed; Bibi, Iram; Ahmad, Zaheer; Yasir, Muhammad

doi:10.1007/s00044-020-02651-z

Cited by 7 publications

(8 citation statements)

References 13 publications

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“…Also, these compounds formed hydrogen bonds with Asn168 and made chelates with both Ni 2+ ions. [ 30 ] Abid et al [ 31 ] reported the most active compounds in creating promising interactions with main amino acids. They also detected that the two Ni 2+ ions accepted chelates with compounds.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermost, Ala169, Met367, His322, and Ala365 create promising interactions with vital parts. [ 31 ] Other previous studies showed that the amino acids counting His322, Met366, Cys321, Ala365, His221, Asn168, Asp362, and Ala169, are accountable for hydrogen bonding. Particularly, the most potent compound showed interactions with significant amino acids counting His221, Cys321, Asp362, and Met366.…”

Section: Resultsmentioning

confidence: 99%

“…[ 32 ] Other similar research studies performed docking studies on different PDB ID, however, they have all mentioned binding compounds to both Ni 2+ ions to display high inhibitory activity. [ 29,31,33,34 ]…”

Section: Resultsmentioning

confidence: 99%

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Design, synthesis, and in silico studies of tetrahydropyrimidine analogs as urease enzyme inhibitors

Ahangarzadeh

Shakour

Rezvanpoor

et al. 2022

Archiv der Pharmazie

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The urease enzyme, a metalloenzyme having Ni 2+ ions, is recognized in some bacteria, fungi, and plants. Particularly, it is vital to the progress of infections induced by pathogenic microbes, such as Proteus mirabilis and Helicobacter pylori. Herein, we reported the synthesis of a series of tetrahydropyrimidine derivatives and evaluated their antiurease activity. Finally, quantitative and qualitative analyses of the derivatives were performed via in silico studies. Urease inhibitory activity was determined as the reaction of H. pylori urease with different concentrations of compounds, and thiourea was used as a standard compound. Docking and dynamics methodologies were applied to study the interactions of the best compounds with the amino acids in the active site. All compounds showed good to excellent antiurease activity. The potent compounds were not cytotoxic against the HUVEC normal cell line. Based on the docking study, compound 4e with the highest urease inhibitory activity (IC 50 = 6.81 ± 1.42 µM) showed chelates with both Ni 2+ ions of the urease active site. Further, compound 4f displayed a very good inhibitory activity (IC 50 = 8.45 ± 1.64 μM) in comparison to thiourea (IC 50 = 22.03 ± 1.24 μM). The molecular docking and dynamics simulation results were correlated with the in vitro assay results. Moreover, the derivatives 4a-n followed Lipinski's rule-of-five and had drug-likeness properties.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Design, synthesis, and in silico studies of tetrahydropyrimidine analogs as urease enzyme inhibitors

Ahangarzadeh

Shakour

Rezvanpoor

et al. 2022

Archiv der Pharmazie

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“…Interacting of compounds with the two Ni 2 + ions in the urease active site plays a main role in the enzyme inhibitory activity. [27,33] This compound formed a hydrogen bond between the amine of Arg338 residue and the oxygen atom of ester moiety (R1), a hydrogen bond between the amine of His221 and the oxygen atom of carbonyl in ester (R1) and a hydrogen bond between the oxygen atom of carbonyl of Met366 and NH of triazole ring of compound 9c. All of these interactions limited the flexibility of the flap region to reduce the enzymatic activity.…”

Section: Molecular Docking Studymentioning

confidence: 99%

Synthesis, Biological Activity Evaluation, Docking and Molecular Dynamics Studies of New Triazole‐Tetrahydropyrimidinone(thione) Hybrid Scaffolds as Urease Inhibitors

Rezvanpoor

Shakour

Ahangarzadeh

et al. 2023

Chemistry & Biodiversity

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New series of triazole-tetrahydropyrimidinone(thione) hybrids (9a -g) were synthesized. FT-IR, 1 H-NMR, 13 C-NMR, elemental analysis and mass spectroscopic studies characterized the structures of the synthesized compounds. Then, the synthesized compounds were screened to determine the urease inhibitory activity. Methyl 4-(4-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5carboxylate (9c) exhibited the highest urease inhibitory activity (IC 50 = 25.02 μM) among the compounds which was almost similar to thiourea as standard (IC 50 = 22.32 μM). The docking study of the screened compounds demonstrated that these compounds fit well in the urease active site. Based on the docking study, compound 9c with the highest urease inhibitory activity showed chelates with both Ni 2 + ions of the urease active site. Moreover, the molecular dynamic study of the most potent compounds showed that they created important interactions with the active site flap residues, His322, Cys321, and Met317.

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“…Recent candidates include tryptamine derivatives (Kanwal et al, 2019), atenolol derivatives (Wahid et al, 2020), Journal of Sustainability Science and Management Volume 17 Number 9, September 2022: 75-95 thiobarbiturate derivatives (Abdulwahab et al, 2020), flavonoid analogues (Liu et al, 2020) and 5,6-dichloro-2-methyl-1H-benzimidazole derivatives (Menteşe et al, 2019), just to name a few. With advances in research technology, computational studies are being increasingly used to search for new urease inhibitors, especially through molecular docking to study the binding interactions and mechanisms (Abid et al, 2021;Ali et al, 2021;Babaee et al, 2021;Taha et al, 2021). While experiments are still the major approach in validating the role of inhibitors, the information provided by molecular docking studies complement experimental results.…”

Section: Introductionmentioning

confidence: 99%

More Than Five Decades of Research on Urease Inhibitors: A Bibliometric Study

Yaakob¹,

ANG²,

Nasir³

et al. 2022

JSSM

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This study focuses on works related to urease inhibitors published from 1970 to 2021, gathered from the Web of Science database. This paper aims to examine the trends of research involving urease inhibitors, as there have been no centralised study that utilises bibliometric methods on the related research fields, methods used, as well as collaborations. The total number of publications examined in this paper after filtering is 574 and the number of review articles on urease inhibitors is on the low side considering other research topics published within the 51-year period. Experimental works are still the core method of gathering information on the usefulness of urease inhibitors in all fields within the investigated time span. From the mid-2000s, theoretical investigations emerged as a complement to experimental research, mostly in the form of molecular docking studies. As in the other fields of study, theoretical works have been accepted as part of research methods to examine the molecular interactions between compounds and urease. The main partners to consider for cooperation in this field of study are those in Pakistan, China, the United States, New Zealand and Spain as their institutions house researchers that are outstanding in the field and they produce articles that are highly cited.

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Synthesis, urease inhibition screening and molecular docking studies of piperonal based imine derivatives

Cited by 7 publications

References 13 publications

Design, synthesis, and in silico studies of tetrahydropyrimidine analogs as urease enzyme inhibitors

Design, synthesis, and in silico studies of tetrahydropyrimidine analogs as urease enzyme inhibitors

Synthesis, Biological Activity Evaluation, Docking and Molecular Dynamics Studies of New Triazole‐Tetrahydropyrimidinone(thione) Hybrid Scaffolds as Urease Inhibitors

More Than Five Decades of Research on Urease Inhibitors: A Bibliometric Study

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