2. Academic Validation
  3. Design, synthesis, and anti-urease evaluations of new sulfonamide-1,2,3-triazole-acetamide derivatives

Design, synthesis, and anti-urease evaluations of new sulfonamide-1,2,3-triazole-acetamide derivatives

  • Sci Rep. 2025 Jul 2;15(1):22565. doi: 10.1038/s41598-025-07553-x.
Shohreh Bakhshi Varzaneh # 1,  Amir Shervin Shokouhi Asl # 2 3,  Mohammad Hosein Sayahi 4,  Amir Mohammad Taherkhani 5,  Meysam Talebi 1,  Navid Dastyafteh 5,  Sajedeh Safapoor 5,  Mehdi Emadi 6,  Majid Alikhani 7,  Rozita Yazzaf 8,  Mohammad Halimi 9,  Massoud Amanlou 1,  Bagher Larijani 5,  Maryam Mohammadi-Khanaposhtani 10,  Mohammad Mahdavi 11
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Student Research Committee, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
  • 4 Department of Chemistry, Payame Noor University, Tehran, Iran.
  • 5 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
  • 6 Electrical and Computer Engineering Department, Babol Noshirvani University of Technology, Babol, Iran.
  • 7 Department of Internal Medicine, School of Medicine, Rheumatology Research Center Shariati Hospital, Tehran University of Medical Sciences,, Tehran, Iran.
  • 8 School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
  • 9 Department of Biology, Babol Branch, Islamic Azad University, Babol, Iran.
  • 10 Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. maryammoha@gmail.com.
  • 11 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. momahdavi@tums.ac.ir.
  • # Contributed equally.
PMID: 40595134 DOI: 10.1038/s41598-025-07553-x
Abstract

The present study demonstrated the design and synthesis of sulfonamide-1,2,3-triazole-acetamide derivatives 11a-o and screening against Urease in vitro and in silico. These compounds were designed based on reported potent Urease inhibitors and optimized structurally based on substituents on acetamide moiety. In vitro studies showed that all the new compounds 11a-o (IC50 values = 0.12-4.53 µM) were more potent than stand inhibitor thiourea (IC50 value = 23.76 µM). In this regard, the most potent compounds were N-phenylacetamide derivatives 11b, 11f, and 11 h with 2-methyl, 4-methoxy, and 2-fluoro substituents, respectively. In this regard, the most potent compound 11b was 198-folds more potent than thiourea against Urease. In silico studies demonstrated that this compound with the binding energy less than thiourea attached to the urease's active site. Druglikeness, pharmacokinetics, and toxicity of compound 11b and thiourea were predicted by two credible online servers. These in silico studies showed that, in terms of druglikeness and pharmacokinetics, compound 11b was almost similar to thiourea while in term of toxicity, compound 11b was better than thiourea.

Keywords

1,2,3-Triazole-acetamide; Sulfonamide; Urease inhibitors.

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