Volume 20, Issue 5 e202300054

Research Article

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

Sadaf Rezvanpoor

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Neda Shakour,

Neda Shakour

Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, 9138813944 Mashhad, Iran

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, 9138813944 Mashhad, Iran

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Nazli Ahangarzadeh,

Nazli Ahangarzadeh

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Hamid Bakherad,

Hamid Bakherad

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran

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Saghi Sepehri,

Corresponding Author

Saghi Sepehri

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Ghazaleh Farhadi,

Ghazaleh Farhadi

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Mohammad Hosein Pakdel,

Mohammad Hosein Pakdel

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran

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Mehrdad Iranshahi,

Mehrdad Iranshahi

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, 9138813944 Mashhad, Iran

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Sadaf Rezvanpoor,

Sadaf Rezvanpoor

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Neda Shakour,

Neda Shakour

Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, 9138813944 Mashhad, Iran

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, 9138813944 Mashhad, Iran

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Nazli Ahangarzadeh,

Nazli Ahangarzadeh

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Hamid Bakherad,

Hamid Bakherad

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran

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Saghi Sepehri,

Corresponding Author

Saghi Sepehri

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Ghazaleh Farhadi,

Ghazaleh Farhadi

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 56189-53141 Ardabil, Iran

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Mohammad Hosein Pakdel,

Mohammad Hosein Pakdel

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, 81746-73461 Isfahan, Iran

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Mehrdad Iranshahi,

Mehrdad Iranshahi

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, 9138813944 Mashhad, Iran

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First published: 07 April 2023

https://doi.org/10.1002/cbdv.202300054

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Abstract

New series of triazole-tetrahydropyrimidinone(thione) hybrids (9a–g) were synthesized. FT-IR, ¹H-NMR, ¹³C-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-5-carboxylate (9c) exhibited the highest urease inhibitory activity (IC₅₀=25.02 μM) among the compounds which was almost similar to thiourea as standard (IC₅₀=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 Ni²⁺ 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.

Graphical Abstract

Conflict of interest

The authors declare no conflict of interest.

Open Research

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Supporting Information

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Volume20, Issue5

May 2023

e202300054

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

Abstract

Graphical Abstract

Conflict of interest

Open Research

Data Availability Statement

Supporting Information

References

References

Information

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

Abstract

Graphical Abstract

Conflict of interest

Open Research

Data Availability Statement

Supporting Information

References

References

Related

Information