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Isoindolin-1-Ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation Publisher



Kazemzadeh H1 ; Hamidian E1 ; Hosseini FS1 ; Abdi M1 ; Niasari Naslaji F1 ; Talebi M1 ; Asadi M1 ; Biglar M3 ; Zarei I1 ; Amanlou M1, 2
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1416634793, Iran
  2. 2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, 1416634793, Iran
  3. 3. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1416634793, Iran

Source: ACS Omega Published:2022


Abstract

Helicobacter pylori-induced ulcers and gastric cancer have been one of the main obstacles that the human community has ever struggled with, especially in recent decades. Several different attempts have been made to eradicate this group. One of the most widely used attempts is to inhibit the critical enzyme that facilitates its survival, the urease enzyme. Therefore, in this study, isoindolin-1-ones fused to barbiturates were designed, synthesized, and evaluated for their in vitro urease inhibitory activity as novel inhibitors for the urease enzyme. The synthesis route consisted of two steps. These steps increased the yield rate and decreased the percentage of byproducts while approaching green chemistry using ethanol and water as green solvents and microwave irradiation instead of conventional methods. In vitro urease inhibitory results indicated that all the compounds had higher inhibitory activity than the standard inhibitor, thiourea, and compound 5b proved to be the most potent inhibitor (IC50= 0.82 ± 0.03 μM). A molecular docking study was performed to understand the interaction between compounds 5a-n and Jack bean urease enzyme. The results of the molecular docking study were also in harmony with the in vitro results, which are discussed in detail later in this study. © 2022 American Chemical Society. All rights reserved.
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