Identification of a C3'-nitrile nucleoside analogue inhibitor of pancreatic cancer cell line growth

Bioorg Med Chem Lett. 2020 Mar 15;30(6):126983. doi: 10.1016/j.bmcl.2020.126983. Epub 2020 Jan 21.

Abstract

A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.

Keywords: Capan2; KRAS mutation; Nucleoside analogues; Pancreatic cancer; Stereogenic quaternary center.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Benzylamines / chemistry
  • Cell Proliferation / drug effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / chemistry
  • Deoxycytidine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Gemcitabine
  • Glycosylation
  • Humans
  • Mutation
  • Nitriles / chemistry*
  • Pancreatic Neoplasms / drug therapy*
  • Phosphoric Acids / chemistry
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Purines / chemistry
  • Structure-Activity Relationship

Substances

  • Amides
  • Antineoplastic Agents
  • Benzylamines
  • KRAS protein, human
  • Nitriles
  • Phosphoric Acids
  • Purines
  • Deoxycytidine
  • phosphoramidic acid
  • benzylamine
  • Proto-Oncogene Proteins p21(ras)
  • purine
  • Gemcitabine