Asgari, M.S. and Azizian, H. and Nazari Montazer, M. and Mohammadi-Khanaposhtani, M. and Asadi, M. and Sepehri, S. and Ranjbar, P.R. and Rahimi, R. and Biglar, M. and Larijani, B. and Amanlou, M. and 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).
Full text not available from this repository.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
| Item Type: | Article |
|---|---|
| Additional Information: | cited By 1 |
| Uncontrolled Keywords: | 1,2,3 triazole derivative; hydroxyurea; thiobarbituric acid derivative; thiourea; urease inhibitor, Ames test; animal cell; Article; computer model; controlled study; drug absorption; drug design; drug distribution; drug excretion; drug metabolism; drug structure; drug synthesis; enzyme active site; enzyme conformation; enzyme inhibitor interaction; enzyme kinetics; human; human cell; IC50; in vitro study; molecular docking; molecular dynamics; mouse; nonhuman; plasma protein binding; prediction; priority journal; rat |
| Subjects: | WB Practice of Medicine |
| Depositing User: | eprints admin |
| Date Deposited: | 29 May 2021 05:38 |
| Last Modified: | 29 May 2021 05:38 |
| URI: | http://eprints.iums.ac.ir/id/eprint/34211 |
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