Synthesis, Biological Activity, and Computational Examination of New 3-Cyano-2-oxa-pyridine Derivatives: http://www.doi.org/10.26538/tjnpr/v7i11.36

Kawkab A Hussein; Zainab Al-Shuhaib; Sadiq M. H. Ismael

Authors

Kawkab A Hussein Department of Chemistry, College of Education for Pure Sciences, University of Basrah, Basrah, Iraq
Zainab Al-Shuhaib Department of Chemistry, College of Education for Pure Sciences, University of Basrah, Basrah, Iraq
Sadiq M. H. Ismael Department of Chemistry, College of Education for Pure Sciences, University of Basrah, Basrah, Iraq

Keywords:

Pharmacokinetics, DFT, Multicomponent reaction, Cyano-pyridines, Anticancer

Abstract

Numerous studies have been carried out into the chemistry of condensed heterocyclic compounds in terms of their medication discovery and various biological properties. Pyridines play an essential role in medicinal chemistry because they are widely available as natural compounds and have served as the foundation for several drugs on the market. In the current investigation, 3-cyano-2-oxa-pyridine derivatives 4a-e were synthesized by a one-pot multicomponent reaction, starting from substituted acetophenone, ethyl cyanoacetate, and aryl aldehydes in the presence of ammonium acetate. All the new products were subjected to proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), two-dimensional (2D)-NMR analysis using heteronuclear single quantum coherence spectroscopy (HSQC), and electron ionization (EI-MS). Additionally, an in vitro cytotoxicity test was performed on cervical carcinoma (HeLa) and cerebral glioblastoma multiforme (AMGM5) cells for every produced molecule. The results indicated that the tested compounds 4a, 4c, and 4e inhibited AMGM5 cells with average IC50 values of 656.4, 781.5, and 374.5 μM, respectively. Compounds 4a, 4b, and 4e, on the other hand, showed a cytotoxic action against the HeLa cell line, with average IC50 values of 558.5, 775.6, and 615.9 μM, respectively. The optimized geometry and reactivity descriptors were also analyzed, including the highest occupied molecular orbital (HOMO), least unoccupied molecular orbital (LUMO), energy band gap (ΔE), chemical potential (µ), electronegativity (χ), chemical hardness (η), chemical softness (S), and electrophilicity (ω). The experimental outcomes of the biological evaluation were consistent with the results of the investigation into their molecular modeling.

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