Synthesis of selective inhibitors against V. cholerae sialidase and human cytosolic sialidase NEU2

Zahra Khedri, Yanhong Li, Hongzhi Cao, Jingyao Qu, Hai Yu, Musleh M. Muthana, Xi Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Sialidases or neuraminidases catalyze the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates. Despite successes in developing potent inhibitors specifically against influenza virus neuraminidases, the progress in designing and synthesizing selective inhibitors against bacterial and human sialidases has been slow. Guided by sialidase substrate specificity studies and sialidase crystal structural analysis, a number of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA or Neu5Ac2en) analogues with modifications at C9 or at both C5 and C9 were synthesized. Inhibition studies of various bacterial sialidases and human cytosolic sialidase NEU2 revealed that Neu5Gc9N32en and Neu5AcN39N 32en are selective inhibitors against V. cholerae sialidase and human NEU2, respectively.

Original languageEnglish (US)
Pages (from-to)6112-6120
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number30
DOIs
StatePublished - Aug 14 2012

Fingerprint

cholera
Cholera
Neuraminidase
inhibitors
synthesis
influenza
acids
viruses
structural analysis
Glycoconjugates
hydrolysis
N-Acetylneuraminic Acid
Substrate Specificity
Orthomyxoviridae
Oligosaccharides
analogs
Hydrolysis
Viruses
Structural analysis
crystals

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Synthesis of selective inhibitors against V. cholerae sialidase and human cytosolic sialidase NEU2. / Khedri, Zahra; Li, Yanhong; Cao, Hongzhi; Qu, Jingyao; Yu, Hai; Muthana, Musleh M.; Chen, Xi.

In: Organic and Biomolecular Chemistry, Vol. 10, No. 30, 14.08.2012, p. 6112-6120.

Research output: Contribution to journalArticle

Khedri, Zahra ; Li, Yanhong ; Cao, Hongzhi ; Qu, Jingyao ; Yu, Hai ; Muthana, Musleh M. ; Chen, Xi. / Synthesis of selective inhibitors against V. cholerae sialidase and human cytosolic sialidase NEU2. In: Organic and Biomolecular Chemistry. 2012 ; Vol. 10, No. 30. pp. 6112-6120.
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