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Synthesis, urease inhibitory and anticancer evaluation of glucosamine-sulfonylurea conjugates

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Abstract

Urease catalyses the hydrolysis of urea to ammonia and carbon dioxide. This enzyme is important in the virulence of several human pathogens and urease activity in soil can cleave urea fertilisers prematurely, leading to waste of agricultural nitrogen. A series of arylsulfonylurea-glucosamine hybrid compounds were synthesised. Reaction of arylsulfonamides with phenyl chloroformate and 4-dimethylaminopyridine gave either phenyl N-(2,4-arylsulfonyl)carbamate 4-dimethylaminopyridinium salts or N-(4-arylsulfonyl)-4-dimethylaminopyridinium-1-carboxamide inner salts, depending on the substitution on the arylsulfonamide. Both types of intermediates, gave ester-protected arylsulfonylurea-glucosamines, when treated with 1,3,4,6-tetra-O-acetylglucosamine. Simple methanolysis gave the arylsulfonylurea-glucosamine hybrids as interconverting mixtures of anomers. Both the O-acetyl intermediates and the target arylsulfonylurea-glucosamines inhibited jack-bean urease with IC50 10–36 μM. This narrow range of values precluded the determination of structure-activity relationships and docking studies suggested several different optimum docking poses for the various analogues. No analogues showed radical-scavenging activity. Several compounds showed modest cytotoxic activity against renal carcinoma cells in the NCI 60-cell-line screen.

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Acknowledgements

The authors would like to acknowledge the Deanship of the Scientific Research for financial support [Grant numbers 2213, 2460] and the support of Dr. Panjwani Center for Molecular Medicine and Drug Research-Pakistan.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, 11942, Jordan

    Ghadeer A. R. Y. Suaifan, Mayadah Shehadeh, Dua’a Tahboub & Aya A. M. Mohammed

  2. Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK

    Michael D. Threadgill

  3. Institute of Biological and Environmental Sciences, Aberystwyth University, Aberystwyth, SY23 3BY, UK

    Michael D. Threadgill

  4. Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, 56000, Malaysia

    Anand Gaurav

  5. Department of Pharmaceutical Sciences and Technology, School of Health Sciences, UPES, Dehradun, 248007, Uttarakhand, India

    Anand Gaurav

  6. Faculty of Health Sciences, Villa College, QI Campus, RahDhebai Hingun, Male, 20373, Republic of Maldives

    Anand Gaurav

  7. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Majid Khan

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Correspondence to Ghadeer A. R. Y. Suaifan.

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Disclosures related to phenylsulfonylurea derivatives of 2-amino-2-deoxy-D-glucopyranose derivatives, their method of preparation, and the use thereof has been registered for patent (Reg. No. PCT/JO2022/050010).

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Suaifan, G.A.R.Y., Shehadeh, M., Tahboub, D. et al. Synthesis, urease inhibitory and anticancer evaluation of glucosamine-sulfonylurea conjugates. Med Chem Res 33, 663–676 (2024). https://doi.org/10.1007/s00044-024-03208-0

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