Imidazo[1,2-a]pyridine moiety is considered a privileged structure in medicinal chemistry due to its broad range of biological activities and drug-like properties. In this work, we carried out a ligand-based similarity search in the Protein Data Bank (PDB) database to identify potential target proteins for a set of imidazo[1,2-a]pyridine derivatives. The ligand-based virtual screening yielded three highly similar compounds with inhibitory activities against phosphoinositide 3-kinase (PI3K), apoptosis signal-regulating kinase 1 (ASK1), and interleukin-1 receptor-associated kinase 4 (IRAK-4). Furthermore, a site-directed molecular docking study showed that our compounds adopt similar binding modes and interactions in the kinase binding sites to that of the reference inhibitors. Ligand-Protein interaction profiles were further analyzed to optimize the initially proposed structures. The new set of imidazo[1,2-a]pyridine derivatives was synthesized as follows: the substituted 2-aminopyridine was treated with neat ethyl bromoacetate and subsequently heated in phosphorus oxychloride to afford the corresponding imidazo[1,2-a]pyridine. Final products were isolated, purified and characterized by spectroscopic and spectrometric techniques. The compounds exhibited moderate to good cytotoxic activities against HeLa, MCF-7, and lung cell lines. Our results suggest that these imidazo[1,2-a]pyridine derivatives are potential protein kinase inhibitors for the treatment of cancer.

Target fishing and synthesis of imidazo[1,2-a]pyridine derivatives as potential cytotoxic agents

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.