Design, synthesis and antitumor activity of phthalazine-1,4-dione-based menaquinone analogs

Bioorg Med Chem Lett. 2021 Jul 1:43:128065. doi: 10.1016/j.bmcl.2021.128065. Epub 2021 Apr 26.

Abstract

New chemotherapeutics are needed to treat hepatocellular carcinoma (HCC), and menaquinones, homologs of vitamin K consisting of a 1,4-naphthoquinone core and a (poly)isoprene chain, are potential candidates. In this study, we designed and synthesized a series of phthalazine-1,4-dione-based menaquinone analogs. Among them, compounds bearing the intact isoprene chain exhibited selective antiproliferative activity towards HCC cell line JHH7, as compared with normal hepatocytes. The geranyl derivative 10 showed submicromolar potency, and might be a promising lead compound for anticancer agents.

Keywords: Antitumor; Menaquinone; Phthalazine; Phthalazine-1,4-dione.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Phthalazines / chemical synthesis
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Structure-Activity Relationship
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / chemical synthesis
  • Vitamin K 2 / chemistry
  • Vitamin K 2 / pharmacology

Substances

  • Antineoplastic Agents
  • Phthalazines
  • Vitamin K 2
  • menatetrenone