Semicarbazone derivatives as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation

Qazi SU 1 , Rahman SU 2 , Awan AN 3 , Al-Rashida M 4 , Alharthy RD 5 , Asari A 6 Show all authors , Hameed A 7 , Iqbal J 8

Affiliations 

  • 1 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Pakistan
  • 2 COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Pakistan
  • 4 Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan
  • 5 Department of Chemistry, Science and Arts College, Rabigh Campus, King Abdulaziz University, Jeddah, Saudi Arabia
  • 6 School of Fundamental Science, Universiti Malaysia Terengganu, 21030 kuala Terengganu, Terengganu, Malaysia
  • 7 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: abdul.hameed@iccs.edu
  • 8 COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: drjamshed@ciit.net.pk
Bioorg Chem, 2018 09;79:19-26.
PMID: 29709568 DOI: 10.1016/j.bioorg.2018.03.029

Abstract

A series of hydrazinecarboxamide derivatives were synthesized and examined against urease for their inhibitory activity. Among the series, the 1-(3-fluorobenzylidene)semicarbazide (4a) (IC50 = 0.52 ± 0.45 µM), 4u (IC50 = 1.23 ± 0.32 µM) and 4h (IC50 = 2.22 ± 0.32 µM) were found most potent. Furthermore, the molecular docking study was also performed to demonstrate the binding mode of the active hydrazinecarboxamide with the enzyme, urease. In order to estimate drug likeness of compounds, in silico ADME evaluation was carried out. All compounds exhibited favorable ADME profiles with good predicted oral bioavailability.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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