New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation

New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation Publisher Pubmed

Asgari MS¹ ; Azizian H² ; Nazari Montazer M³ ; Mohammadikhanaposhtani M⁴ ; Asadi M³ ; Sepehri S⁵ ; Ranjbar PR¹ ; Rahimi R⁶ ; Biglar M⁷ ; Larijani B⁷ ; Amanlou M³ ; Mahdavi M⁷

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1. School of Chemistry, College of Science, University of Tehran, Tehran, Iran
2. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran
3. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
4. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
5. Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
6. Department of Chemistry, Iran University of Science and Technology, Tehran, Iran
7. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Archiv der Pharmazie Published:2020

Abstract

A new series of 1,2,3-triazole–(thio)barbituric acid hybrids 8a–n was designed and synthesized on the basis of potent pharmacophores with urease inhibitory activity. Therefore, these compounds were evaluated against Helicobacter pylori urease. The obtained result demonstrated that all the synthesized compounds, 8a–n, were more potent than the standard urease inhibitor, hydroxyurea. Moreover, among them, compounds 8a, 8c–e, 8g,h, and 8k,l exhibited higher urease inhibitory activities than the other standard inhibitor used: thiourea. Docking studies were performed with the synthesized compounds. Furthermore, molecular dynamic simulation of the most potent compounds, 8e and 8l, showed that these compounds interacted with the conserved residues Cys592 and His593, which belong to the active site flap and are essential for enzymatic activity. These interactions have two consequences: (a) blocking the movement of a flap at the entrance of the active site channel and (b) stabilizing the closed active site flap conformation, which significantly reduces the catalytic activity of urease. Calculation of the physicochemical and topological properties of the synthesized compounds 8a–n predicted that all these compounds can be orally active. The ADME prediction of compounds 8a–n was also performed. © 2020 Deutsche Pharmazeutische Gesellschaft

Style	Citing Format
MLA	Asgari MS, et al.. "New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation." Archiv der Pharmazie, vol. 353, no. 9, 2020, pp. -.
APA	Asgari MS, Azizian H, Nazari Montazer M, Mohammadikhanaposhtani M, Asadi M, Sepehri S, Ranjbar PR, Rahimi R, Biglar M, Larijani B, Amanlou M, Mahdavi M (2020). New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation. Archiv der Pharmazie, 353(9), -.
Chicago	Asgari MS, Azizian H, Nazari Montazer M, Mohammadikhanaposhtani M, Asadi M, Sepehri S, Ranjbar PR, et al.. "New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation." Archiv der Pharmazie 353, no. 9 (2020): -.
Harvard	Asgari MS et al. (2020) 'New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation', Archiv der Pharmazie, 353(9), pp. -.
Vancouver	Asgari MS, Azizian H, Nazari Montazer M, Mohammadikhanaposhtani M, Asadi M, Sepehri S, et al.. New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation. Archiv der Pharmazie. 2020;353(9):-.
BibTex	@article{ author = {Asgari MS and Azizian H and Nazari Montazer M and Mohammadikhanaposhtani M and Asadi M and Sepehri S and Ranjbar PR and Rahimi R and Biglar M and Larijani B and Amanlou M and Mahdavi M}, title = {New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation}, journal = {Archiv der Pharmazie}, volume = {353}, number = {9}, pages = {-}, year = {2020} }
RIS	TY - JOUR AU - Asgari MS AU - Azizian H AU - Nazari Montazer M AU - Mohammadikhanaposhtani M AU - Asadi M AU - Sepehri S AU - Ranjbar PR AU - Rahimi R AU - Biglar M AU - Larijani B AU - Amanlou M AU - Mahdavi M TI - New 1,2,3-Triazole–(Thio)Barbituric Acid Hybrids As Urease Inhibitors: Design, Synthesis, in Vitro Urease Inhibition, Docking Study, and Molecular Dynamic Simulation JO - Archiv der Pharmazie VL - 353 IS - 9 SP - EP - PY - 2020 ER -

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