Synthesis and Cytotoxicity of Some Imidazo[4, 5‐b]pyridine Derivatives and Their Regioselective N‐Alkylation. Issue 7 (15th February 2021)

• Record Type: Journal Article
• Authors: Doganc, Fatima; Alp, Mehmet; Karabay, Arzu; Koç, Aslı; Eren, Gokcen; Göker, Hakan
• Is Part Of: ChemistrySelect. Volume 6:Issue 7(2021)
• Page Start: 1519
• Page End: 1525
• Publication Date: 2021-02-15
• Subjects: 1H-15N HMBC -- Biological activity -- Imidazopyridine-2-carboxamides -- NMR spectroscopy -- Regioisomer; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202004584
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Some 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 (K2 CO3, 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 1 H− 1 H NOE (Nuclear overhauser effect spectroscopy, NOESY) and 1 H/ 13 C‐ 15 N HMBC (Heteronuclear Multiple Bond Correlation) experiments. We observed that, N ‐benzylation occurs at a higher ratio on the pyridine moiety as N 4 ‐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. Abstract : In this work some of the imidazopyridines bearing the amide and amidoxime groups were synthesized for developing new anticancer agents. Since the imidazopyridine ring exist in three tautomeric forms, N ‐alkylation with benzyl bromide under basic conditions formed the mixture of three regioisomers. Their structural assignments were made with two‐dimensional 1 H‐ 1 H NOE (Nuclear overhauser effect spectroscopy, NOESY) and 1 H/ 13 C‐ 15 N HMBC (Heteronuclear Multiple Bond Correlation) experiments. We observed that N ‐benzylation occurs at a higher ratio on the pyridine moiety as N 4 ‐regiosomer.