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

Ghadeer A.R.Y. Suaifan, Mayadah Shehadeh, Dua’a Tahboub, Aya A.M. Mohammed, Michael D. Threadgill, Anand Gaurav, Majid Khan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)663-676
Number of pages14
JournalMedicinal Chemistry Research
Volume33
Issue number4
Early online date7 Mar 2024
DOIs
Publication statusPublished - 30 Apr 2024

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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