Citation: Rahim Fazal, Ali Muhammad, Ullah Shifa, Rashid Umer, Ullah Hayat, Taha Muhammad, Javed Muhammad Tariq, Rehman Wajid, Khan Aftab Ahmad, Abid Obaid Ur Rahman, Bilal Muhammad. Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies[J]. Chinese Chemical Letters, ;2016, 27(5): 693-697. doi: 10.1016/j.cclet.2015.12.035 shu

Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies

a.
Department of Chemistry, Hazara University, Mansehra 21120, Khyber Pukhtankhwa, Pakistan
b.
Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, KPK, Pakistan
c.
Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
d.
Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA(UiTM), PuncakAlam Campus, 42300 Bandar PuncakAlam, Selangor DarulEhsan, Malaysia
e.
Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia
f.
Department of Environmental Science, COMSATS Institute of Information Technology, Abbottabad 22060, KPK, Pakistan

Corresponding author: Rahim Fazal, fazalstar@gmail.com Ali Muhammad, muhammad_ali@ciit.net.pk
Received Date: 17 August 2015
Revised Date: 25 October 2015
Accepted Date: 30 December 2015
Available Online: 25 May 2016

Figures(4)

Bis-thiobarbiturate derivatives 1-15 have been synthesized, characterized by ¹HNMR and EI-MS and screened for urease inhibition. All compounds showed various degree of urease inhibitory activity with IC₅₀ values ranging 7.45±0.12-74.24±0.81 μmol/L while the standard thiourea behaved normally (IC₅₀=21.10±0.12). Compounds 1 (IC₅₀=7.45±0.12 μmol/L), 9 (IC₅₀=18.17±1.03 μmol/L) and 13 (IC₅₀=8.61±0.45 μmol/L) showed excellent urease inhibitory activity in the series. Molecular modeling studies were performed to understand the binding site with the bimetallic nickel center of the enzyme. Structure-activity relationship has also been established for these compounds. This study identified bisthiobarbiturate as a novel class of urease inhibitors.
- Thiobarbituric acid,
- Synthesis,
- Urease inhibition,
- Molecular docking studies
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