N‐Aroyl‐N′‐(1‐Naphthyl)‐N′′‐aryl guanidines as a New Entry to Urease Inhibitors: Synthesis, Kinetic Mechanism, Molecular Docking and MD Simulation Studies

Author:

Tahira Sarwat1,Saeed Aamer1ORCID,Farid Aftab1,Channar Pervaiz Ali12,Tehzeeb Arfa1,Abbas Qamar3,Abdalla Mohnad4

Affiliation:

1. Department of Chemistry Quaid-i-Azam University 45320 Islamabad Pakistan

2. Department of Basic Sciences and Humanities Faculty of Information Science and Humanities Dawood University of Engineering and Technology 74800 Karachi Pakistan

3. Department of Biology College of Science University of Bahrain Sakhir Campus 32038 Sakhir Bahrain

4. Qingdao Institute of Bioenergy and Bioprocess Technology 266000 Qingdao Shi Shandong Sheng People's Republic of China

Abstract

AbstractA series of novel guanidines (6 aj) was synthesized from corresponding thioureas using catalytic mercuric chloride in DMF. The synthesized compounds were characterized by spectroscopic techniques and appraised for Jack Bean Urease (JBU) inhibition. All compounds (6 aj) exhibited strong potential against JBU whilst compound 6 b (IC50=0.0155±0.00087 μM) and 6 e (IC50=0.0091±0.00036 μM) displayed excellent urease inhibition compared to thiourea (IC50=18.27 μM) used as reference. The kinetic mechanism analyzed by Lineweaver‐Burk plots revealed that 6 b is a mixed‐type inhibitor while 6 e is a non‐competitive inhibitor. Thus, compounds 6 e and 6 b can serve as a structural model for the designing of super‐effective urease inhibitors. Binding affinity and interaction of N‐aryl guanidine analogs were evaluated through molecular docking studies. To evaluate the residual flexibility of receptor through MD simulation, RMSD and RMSF graphs were evaluated to determine the protein structural behavior. It is implied that compound 6 e can serve as a novel molecular template to medicinal chemists for designing more potent urease inhibitors.

Publisher

Wiley

Subject

General Chemistry

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3