Design, synthesis and anti-tumor activity studies of novel pyrido[3, 4-d]pyrimidine derivatives

Bioorg Med Chem Lett. 2022 Nov 15:76:129020. doi: 10.1016/j.bmcl.2022.129020. Epub 2022 Oct 8.

Abstract

In order to find high-efficiency and low-toxic anti-tumor drugs, 29 pyrido[3,4-d]pyrimidine compounds were designed, synthesized and evaluated by MTT assay in vitro. The results presented that most of the compounds had good antitumor activities, among which compound 30 had the best anti-tumor activity on MGC803 cells (IC50 = 0.59 μM). Mechanistic studies exhibited that compound 30 inhibited migration of MGC803 and induced apoptosis. It was proved that compound 30 up-regulated expression of Bid and PARP, down-regulated expression of CycD1 by western blot experiments. This study indicated that compound 30 might be served as a lead agent for the treatment of human gastric cancers.

Keywords: Antitumor activity; Apoptosis; Proliferation; Pyrido[3,4-d]pyrimidine derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / pharmacology
  • Apoptosis* / drug effects
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • Cell Line, Tumor
  • Humans
  • Poly(ADP-ribose) Polymerases / metabolism
  • Pyrimidines* / chemical synthesis
  • Pyrimidines* / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Poly(ADP-ribose) Polymerases
  • BH3 Interacting Domain Death Agonist Protein