Synthesis and in vitro urease inhibitory activity of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides, in silico and kinetic studies

  • Bioorg Chem. 2022 Mar;120:105592. doi: 10.1016/j.bioorg.2021.105592.
Mehdi Asadi  1 ,  Aida Iraji  2 ,  Maede Sherafati  3 ,  Mohammad Nazari Montazer  3 ,  Shirin Ansari  4 ,  Maryam Mohammadi Khanaposhtani  5 ,  Nader Tanideh  6 ,  Mehdi Dianatpour  6 ,  Mahmood Biglar  7 ,  Bagher Larijani  7 ,  Alireza Foroumadi  3 ,  Homa Azizian  7 ,  Massoud Amanlou  8 ,  Mohammad Mahdavi  9
Affiliations
  • 1. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 2. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran; Liosa Pharmed Parseh Company, Shiraz, Iran.
  • 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 4. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 5. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
  • 6. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 7. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 8. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
  • 9. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
PMID: 35121554 DOI: 10.1016/j.bioorg.2021.105592
Abstract

A series of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides were rationally designed and synthesized. All synthetic compounds were evaluated for their Urease inhibitory activity and exhibited good inhibitory potential against Urease with IC50 values in the range of 0.94 - 6.78 μM as compared to the standard thiourea (IC50 = 22.50 μM). Compound 8g (IC50 = 0.94 μM) with a thiophene substituent at the R2 position was found to be the most active member of the series. Kinetic studies exhibited that the compound 8g was a non-competitive inhibitor. In silicostudy showed the critical interactions of potent inhibitors with the active site of the enzyme. These newly identified inhibitors of the Urease enzyme can serve as leads for further research and development.

Keywords
5-Nitrofuran-2-yl-thiadiazole; Cyclohexyl-2-(phenylamino)acetamides; Docking; Synthesis; Urease.
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