Hydrophobic benzoic acids as inhibitors of influenza neuraminidase.

Academic Article

Abstract

  • Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC50 1 microM) over type B (B/Lee/40) influenza NA (IC50 500 microM).
  • Published In

    Keywords

  • Antiviral Agents, Benzoates, Crystallography, X-Ray, Enzyme Inhibitors, Models, Molecular, Neuraminidase, Orthomyxoviridae, Protein Conformation
  • Author List

  • Atigadda VR; Brouillette WJ; Duarte F; Babu YS; Bantia S; Chand P; Chu N; Montgomery JA; Walsh DA; Sudbeck E
  • Start Page

  • 2487
  • End Page

  • 2497
  • Volume

  • 7
  • Issue

  • 11