Synthesis, Biological Activity, and Computational Examination of New 3-Cyano-2-oxa-pyridine Derivatives

Abstract

3-Cyano-2-pyridones are analogous to the alkaloid ricinine, the first known alkaloid that contains a cyano group. The anticancer activity of 3-cyano-2-pyridone derivatives is exciting due to the numerous biological targets they may interact with, including phosphodiesterase 3 and the provirus integration site for the Moloney murine leukaemia virus-1 kinase and survival. 18,19 Encouraged by recent literature observations, some new pyridine derivatives were synthesised in this study, resulting in fascinating heterocyclic frameworks that are most beneficial for the construction of various chemical libraries of compounds with a variety of functional groups for examining unique biological agents. This study was aimed at synthesising new 3-cyano-2-oxa-pyridine derivatives (4a-e) using substituted acetophenone, ethyl cyanoacetate, and aryl aldehydes in the presence of ammonium acetate. Moreover, they demonstrated anticancer efficacy against two cancer cell lines, namely cerebral glioblastoma multiforme and cervical carcinoma. The variations in biological activity induced by changes in the positions of substituted groups like H, Br, NH2, and OCH3 were explored as an outcome of this research. The synthesised compounds were subjected to theoretical calculations using the density-functional theory (DFT), an adverse medical device event (AMDE) assay, and by making comparisons with experimental data. These studies will provide insight into the molecular properties of novel pyridine derivatives. Materials and Methods Sources for cell lines and maintenance of cell culturesTwo cancer cell lines, namely cerebral glioblastoma multiforme (AMGM5) and cervical carcinoma (HeLa), were purchased from the IRAQ Biotechnology Cell Banking Centre in Basrah and grown in RPMI-1640 treated with 10% foetal bovine serum, 100 units/mL of the antibiotic penicillin, and 100 g/mL of minocycline. The cells were