title: Design of new and potent diethyl thiobarbiturates as urease inhibitors: a computational approach.
abstract: Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP) urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands.. The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully identify potential drug candidates.
authors: Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
authors: Abdul
authors: A
authors: Wadood
authors: Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
authors: Muhammad
authors: M
authors: Riaz
authors: Department of Chemistry, Abdul Wali Khan University Mardan, Pakistan.
authors: Amir Ul
authors: AU
authors: Mulk
authors: Department of Chemistry, Abdul Wali Khan University Mardan, Pakistan.
authors: Momin
authors: M
authors: Khan
authors: National Center of Excellence in Molecular Biology, University Punjab Lahore, Pakistan.
authors: Sobia Ahsan
authors: SA
authors: Haleem
authors: Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
authors: Sulaiman
authors: S
authors: Shams
authors: Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
authors: Sahib
authors: S
authors: Gul
authors: Department of Biotechnology, Abdul Wali Khan University Mardan, Pakistan.
authors: Ayaz
authors: A
authors: Ahmed
authors: Department of Environmental Sciences, Abdul Wali Khan University Mardan, Pakistan.
authors: Muhammad
authors: M
authors: Qasim
authors: Department of Zoology, Abdul Wali Khan University Mardan, Pakistan.
authors: Farman
authors: F
authors: Ali
authors: HEJ, Research Institute of Chemistry, University of Karachi, Karachi, Pakistan.
authors: Zaheer
authors: Z
authors: Ul-Haq
keywords: H. pylori; Interaction energy; MOE; Molecular docking; Urease Inhibitor