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

Kahriman N., Peker K., Serdaroğlu V., Aydin A., Usta A., Fandakli S., ...More

BIOORGANIC CHEMISTRY, vol.99, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 99
  • Publication Date: 2020
  • Doi Number: 10.1016/j.bioorg.2020.103805
  • Journal Name: BIOORGANIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: 2-Amino-4-aryl-6-pyridopyrimidine, N-alkyl bromide, Anti-proliferative effect, Cytotoxic effect, Antibacterial activity, DNA/protein binding affinity, 2,4,6-TRISUBSTITUTED PYRIMIDINES, ANTIMICROBIAL ACTIVITY, BIOLOGICAL EVALUATION, ANTIMALARIAL ACTIVITY, ASSISTED SYNTHESIS, EFFICIENT, CYTOTOXICITY, HETEROCYCLES, CARBAZOLE, COMPLEXES
  • Recep Tayyip Erdoğan University Affiliated: Yes

Abstract

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.