Kazemzadeh Houman, Hamidian Elham, Hosseini Faezeh Sadat, Abdi Movahed, Niasari Naslaji Fatemeh, Talebi Meysam, Asadi Mehdi, Biglar Mahmood, Zarei Issa, Amanlou Massoud
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1416634793, Iran.
The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1416634793, Iran.
ACS Omega. 2022 Jun 2;7(23):19401-19411. doi: 10.1021/acsomega.2c01028. eCollection 2022 Jun 14.
-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 proved to be the most potent inhibitor (IC = 0.82 ± 0.03 μM). A molecular docking study was performed to understand the interaction between compounds 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.
幽门螺杆菌诱导的溃疡和胃癌一直是人类社会面临的主要难题之一，尤其是在近几十年。人们进行了多种不同尝试来根除这一群体。其中一种应用最为广泛的尝试是抑制促进其存活的关键酶——脲酶。因此，在本研究中，设计、合成了与巴比妥类药物融合的异吲哚啉 - 1 - 酮，并对其作为脲酶新型抑制剂的体外脲酶抑制活性进行了评估。合成路线包括两个步骤。这些步骤提高了产率，降低了副产物的比例，同时以乙醇和水作为绿色溶剂，采用微波辐射而非传统方法，朝着绿色化学的方向发展。体外脲酶抑制结果表明，所有化合物的抑制活性均高于标准抑制剂硫脲，化合物 被证明是最有效的抑制剂（IC = 0.82 ± 0.03 μM）。进行了分子对接研究以了解化合物 与刀豆脲酶之间的相互作用。分子对接研究的结果也与体外结果一致，本研究稍后将详细讨论。
