Display options
Cite
Wadood A, Riaz M, Mulk AU, et al. Design of new and potent diethyl thiobarbiturates as urease inhibitors: a computational approach. Bioinformation. 2014;10(5):299-307doi: 10.6026/97320630010299.
Wadood, A., Riaz, M., Mulk, A. U., Khan, M., Haleem, S. A., Shams, S., Gul, S., Ahmed, A., Qasim, M., Ali, F., & Ul-Haq, Z. (2014). Design of new and potent diethyl thiobarbiturates as urease inhibitors: a computational approach. Bioinformation, 10(5), 299-307. https://doi.org/10.6026/97320630010299
Wadood, Abdul, et al. "Design of new and potent diethyl thiobarbiturates as urease inhibitors: a computational approach." Bioinformation vol. 10,5 (2014): 299-307. doi: https://doi.org/10.6026/97320630010299
Wadood A, Riaz M, Mulk AU, Khan M, Haleem SA, Shams S, Gul S, Ahmed A, Qasim M, Ali F, Ul-Haq Z. Design of new and potent diethyl thiobarbiturates as urease inhibitors: a computational approach. Bioinformation. 2014 May 20;10(5):299-307. doi: 10.6026/97320630010299. eCollection 2014. PMID: 24966538; PMCID: PMC4070040.
Copy Download .nbib Format: NLM
Share it on

Bioinformation. 2014 May 20;10(5):299-307. doi: 10.6026/97320630010299. eCollection 2014.

Design of new and potent diethyl thiobarbiturates as urease inhibitors: a computational approach.

Bioinformation

Abdul Wadood, Muhammad Riaz, Amir Ul Mulk, Momin Khan, Sobia Ahsan Haleem, Sulaiman Shams, Sahib Gul, Ayaz Ahmed, Muhammad Qasim, Farman Ali, Zaheer Ul-Haq

Affiliations

  1. Computational Medicinal Chemistry Laboratory, Department of Biochemistry, Abdul Wali Khan University, Mardan, Pakistan.
  2. Department of Chemistry, Abdul Wali Khan University Mardan, Pakistan.
  3. National Center of Excellence in Molecular Biology, University Punjab Lahore, Pakistan.
  4. Department of Biotechnology, Abdul Wali Khan University Mardan, Pakistan.
  5. Department of Environmental Sciences, Abdul Wali Khan University Mardan, Pakistan.
  6. Department of Zoology, Abdul Wali Khan University Mardan, Pakistan.
  7. HEJ, Research Institute of Chemistry, University of Karachi, Karachi, Pakistan.

PMID: 24966538 PMCID: PMC4070040 DOI: 10.6026/97320630010299

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.

Keywords: H. pylori; Interaction energy; MOE; Molecular docking; Urease Inhibitor

References

  1. Microbiol Rev. 1989 Mar;53(1):85-108 - PubMed
  2. J Biol Inorg Chem. 2000 Feb;5(1):110-8 - PubMed
  3. ACS Med Chem Lett. 2010 May 10;1(4):145-9 - PubMed
  4. J Biol Inorg Chem. 2001 Mar;6(3):300-14 - PubMed
  5. Plant Physiol. 1995 Apr;107(4):1097-103 - PubMed
  6. J Am Chem Soc. 1975 Jul 9;97(14):4131-3 - PubMed
  7. J Comput Chem. 2008 Jul 30;29(10):1693-8 - PubMed
  8. J Mol Graph Model. 2013 Mar;40:40-7 - PubMed
  9. Eur J Cancer Prev. 1998 Dec;7(6):439-47 - PubMed
  10. Structure. 1999 Feb 15;7(2):205-16 - PubMed
  11. Cancer. 1998 Nov 15;83(10):2049-53 - PubMed
  12. J Natl Cancer Inst. 1993 Sep 15;85(18):1483-92 - PubMed
  13. J Mol Graph Model. 2011 Sep;30:153-6 - PubMed
  14. J Am Chem Soc. 2004 Mar 31;126(12):3714-5 - PubMed
  15. Lancet. 1975 Jul 12;2(7924):58-60 - PubMed
  16. Br Med Bull. 1998;54(1):151-62 - PubMed
  17. Epidemiol Rev. 1986;8:1-27 - PubMed

Publication Types