Development of novel DIF-1 derivatives that selectively suppress innate immune responses

Bioorg Med Chem. 2015 Aug 1;23(15):4311-4315. doi: 10.1016/j.bmc.2015.06.027. Epub 2015 Jun 17.

Abstract

The multiple pharmacological activities of differentiation-inducing factor-1 (DIF-1) of the cellular slime mold Dictyostelium discoideum led us to examine the use of DIF-1 as a 'drug template' to develop promising seed compounds for drug discovery. DIF-1 and its derivatives were synthesized and evaluated for their regulatory activities in innate immune responses. We found two new derivatives (4d and 5e) with highly selective inhibitory activities against production of the antimicrobial peptide attacin in Drosophila S2 cells and against production of interleukin-2 in Jurkat cells.

Keywords: Cellular slime mold; Drosophila; Immunosuppressor; Innate immunity; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Benzene / chemistry
  • Chemistry Techniques, Synthetic
  • Dictyostelium
  • Drosophila / cytology
  • Drosophila / immunology
  • Drug Discovery
  • Drug Evaluation, Preclinical / methods
  • Hexanones / chemistry*
  • Hexanones / pharmacology
  • Humans
  • Immunity, Innate / drug effects*
  • Immunosuppressive Agents / chemistry*
  • Immunosuppressive Agents / pharmacology*
  • Insect Proteins / metabolism
  • Interleukin-2 / metabolism
  • Jurkat Cells / drug effects
  • Jurkat Cells / metabolism

Substances

  • Hexanones
  • Immunosuppressive Agents
  • Insect Proteins
  • Interleukin-2
  • attacin antibacterial protein, insect
  • 1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone
  • Benzene