Synthesis and Cytotoxicity of Some Imidazo[4,5-b]pyridine Derivatives and Their Regioselective N-Alkylation

Doganc F., Alp M., Karabay A., Koç A., EREN G., Göker H.

ChemistrySelect, vol.6, no.7, pp.1519-1525, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 6 Issue: 7
  • Publication Date: 2021
  • Doi Number: 10.1002/slct.202004584
  • Journal Name: ChemistrySelect
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Page Numbers: pp.1519-1525
  • Keywords: H-1-N-15 HMBC, Biological activity, Imidazopyridine-2-carboxamides, NMR spectroscopy, Regioisomer
  • Gazi University Affiliated: Yes


© 2021 Wiley-VCH GmbHSome imidazopyridine-carboxamides and carboximidamides were synthesized and their cytotoxic activities were tested against human leukemia cell lines (K562 and HL-60), human colon cancer cell line (HCT-116), human multiple myeloma cell lines (U266 and H929) and normal mouse fibroblast cell line (L929) by MTT (Tetrazolium salt colorimetric assay). Among them, imidazopyridine-2-phenylcarboxamide analogues 21 a–23, gave the lowest IC50 value with the range of 5.9–9.8 μM. Since the imidazopyridine ring exist in three tautomeric forms, N-alkylation with benzyl bromide under basic conditions (K2CO3, in DMF) formed the mixture of three regioisomers. Their structural assignments (16 a, 20 a, 16 b, 20 b–22 b and 16 c) were made with the use of two-dimensional 1H−1H NOE (Nuclear overhauser effect spectroscopy, NOESY) and 1H/13C-15N HMBC (Heteronuclear Multiple Bond Correlation) experiments. We observed that, N-benzylation occurs at a higher ratio on the pyridine moiety as N4-regiosomer. In order to analyze the possible interactions of compounds 21 a–23, which were found to display good cytotoxic effect against the cancer cell lines tested were selected to dock into Aurora A kinase (AURKA) active site. The results reported that the compounds occupied the ATP pocket via forming interactions with Lys141, Lys162, Thr217, and Tyr 219 indicating the binding affinity to the AURKA.