2. Academic Validation
  3. Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis

Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis

  • Sci Rep. 2021 Sep 23;11(1):18973. doi: 10.1038/s41598-021-98413-x.
Asad Hamad 1,  Mohsin Abbas Khan 1,  Irshad Ahmad 1,  Ruqaiya Khalil 2,  Muhammad Khalid 3,  Urva Abbas 4,  Rahat Azhar 5,  Jalal Uddin 6,  Gaber El-Saber Batiha 7,  Ajmal Khan 8,  Zahid Shafiq 9,  Ahmed Al-Harrasi 10
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
  • 2 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
  • 3 Department of Chemistry, Khwaja Fareed University of Engineering and Information Technology, Rahim Yar Khan, 64200, Pakistan.
  • 4 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan.
  • 5 Islam College of Pharmacy, Sialkot, Pakistan.
  • 6 Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia.
  • 7 Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.
  • 8 Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, P.O Box 33, 616, Nizwa, Oman. ajmalkhan@unizwa.edu.om.
  • 9 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. zahidshafiq@bzu.edu.pk.
  • 10 Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, P.O Box 33, 616, Nizwa, Oman. aharrasi@unizwa.edu.om.
PMID: 34556784 DOI: 10.1038/s41598-021-98413-x
Abstract

Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease Enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of Enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease Enzyme. The synthesized sulphadiazine derivatives (3a-u) were found to be non-toxic, and presented passive gastrointestinal absorption.

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