2. Academic Validation
  3. Benzofuro[3,2-d]pyrimidines inspired from cercosporamide CaPkc1 inhibitor: Synthesis and evaluation of fluconazole susceptibility restoration

Benzofuro[3,2-d]pyrimidines inspired from cercosporamide CaPkc1 inhibitor: Synthesis and evaluation of fluconazole susceptibility restoration

  • Bioorg Med Chem Lett. 2018 Jul 15;28(13):2250-2255. doi: 10.1016/j.bmcl.2018.05.044.
Viet Hung Dao 1,  Isabelle Ourliac-Garnier 2,  Marc-Antoine Bazin 1,  Catherine Jacquot 2,  Blandine Baratte 3,  Sandrine Ruchaud 3,  Stéphane Bach 3,  Olivier Grovel 4,  Patrice Le Pape 2,  Pascal Marchand 5
Affiliations

Affiliations

  • 1 Université de Nantes, Nantes Atlantique Universités, Département de Chimie Thérapeutique, EA1155 - IICiMed, Institut de Recherche en Santé 2, F-44200 Nantes, France.
  • 2 Université de Nantes, Nantes Atlantique Universités, Département de Parasitologie et Mycologie Médicale, EA1155 - IICiMed, Institut de Recherche en Santé 2, F-44200 Nantes, France.
  • 3 Sorbonne Université, CNRS, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), USR Protein Phosphorylation and Human Diseases, Station Biologique, Place Georges Teissier, F-29688 Roscoff, France.
  • 4 Université de Nantes, Nantes Atlantique Universités, EA2160 - Mer Molécules Santé, Faculté de Pharmacie, F 44035 Nantes, France.
  • 5 Université de Nantes, Nantes Atlantique Universités, Département de Chimie Thérapeutique, EA1155 - IICiMed, Institut de Recherche en Santé 2, F-44200 Nantes, France. Electronic address: [email protected].
PMID: 29853332 DOI: 10.1016/j.bmcl.2018.05.044
Abstract

In a context of growing resistance to classical Antifungal therapy, the design of new drugs targeting alternative pathways is highly expected. Benzofuro[3,2-d]pyrimidine derivatives, derived from (-)-cercosporamide, were synthesized and evaluated as potential Candida albicans PKC inhibitors in the aim of restoring susceptibility to azole treatment. Co-administration assay of benzofuropyrimidinedione 23 and fluconazole highlighted a synergistic effect on inhibition of cell growth of a Candida albicans resistant strain.

Keywords

Antifungal activity; Benzofuro[3,2-d]pyrimidine; Candida albicans Pkc1; Cercosporamide; Fluconazole susceptibility restoration.

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