Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents

•Novel series of pyridines heterocyclic compounds were synthesized and characterized.•Optimization of the geometric shape was carried out.•Molecular parameters were calculated.•The biological activities of the synthesized compounds were investigated.

This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, 1H NMR, 13C NMR and MS studies.Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a–d gave the corresponding 2-pyridone derivatives 5–10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, 1H NMR, 13C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having –N(CH3)2 group are most effective.

Graphical abstractNovel series of pyridines heterocyclic compounds have been synthesized and characterized by elemental analyses and spectral like IR, 1H NMR, 13C NMR and MS studies. The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. The biological activities including Anti-tumor, Anti-inflammatory and analgesic activities were investigated. SAR was investigatedFigure optionsDownload full-size imageDownload as PowerPoint slide