Novel 2-amino-4-aryl-6-pyridopyrimidines and N-alkyl derivatives: Synthesis, characterization and investigation of anticancer, antibacterial activities and DNA/BSA binding affinities

KAHRİMAN N., Peker K., SERDAROĞLU V., Aydin A., USTA A. , Fandakli S., ...More

BIOORGANIC CHEMISTRY, vol.99, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 99
  • Publication Date: 2020
  • Doi Number: 10.1016/j.bioorg.2020.103805
  • Title of Journal : BIOORGANIC CHEMISTRY


A series of new 2-amino-4-aryl-6-pyridopyrimidines, and their N-alkyl bromide derivatives were designed and synthesized by employing methyl substituted azachalcones. These novel compounds were evaluated and compared to the well-known chemotherapeutics in terms of their anti-cancer and anti-microbial functions, and their DNA/protein binding affinities. In order for the cell proliferation, cytotoxicity and microdilution features to be observed, various cancer cell lines (Hep3B, A549, HeLa, C6, HT29, MCF7) were treated with 2-amino-4-aryl-6-pyridopyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c, 5a-c, 6a-c, 8a-c, 9a-c). Studies on the cells revealed that both pyrimidines and their alkyl derivatives (i) have a high anti-proliferative and antimicrobial activities, (ii) cause cell rounding, cytoplasmic blebs, and anomalous globular structure, and (iii) strongly bound to DNA/BSA macromolecules. Especially the length of the alkyl chain of the N-alkyl bromides has an increasing effect on the antiproliferative, antibacterial and cytotoxic functions, also DNA/protein binding affinity. Those results indicate the novel compounds to be promising antiproliferative agents, and their anticancer potential makes them candidates to be used for cancer therapy.