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Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4-Triazole Derivatives As Novel Potent Urease Inhibitors: Proposing Repositioning Candidate Publisher Pubmed



Salehi Ashani R1 ; Azizian H2 ; Sadeghi Alavijeh N1 ; Fathi Vavsari V1 ; Mahernia S3 ; Sheysi N4 ; Biglar M3 ; Amanlou M3, 4 ; Balalaie S1, 5
Authors

Source: Chemistry and Biodiversity Published:2020


Abstract

A series of new deferasirox derivatives were synthesized through the reaction of monosubstituted hydrazides with 2-(2-hydroxyphenyl)-4H-benzo[e][1,3]oxazin-4-one. For the first time, deferasirox and some of its derivatives were evaluated for their in vitro inhibitory activity against Jack bean urease. The potencies of the members of this class of compounds are higher than that of acetohydroxamic acid. Two compounds, bearing tetrazole and hydrazine derivatives (bioisoester of carboxylate group), represented the most potent urease inhibitory activity with IC50 values of 1.268 and 3.254 μm, respectively. In silico docking studies were performed to delineate possible binding modes of the compounds with the enzyme, urease. Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its crucial amino acid residues, CME592 and His593. The overall results of urease inhibition have shown that these target compounds can be further optimized and developed as a lead skeleton for the discovery of novel urease inhibitors. © 2020 Wiley-VHCA AG, Zurich, Switzerland
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