Novel oxadiazolyl-thio and triazolyl-thio-heterocylces: Synthesis, characterization, and In Silico Screening for Targeting NF-κB in Breast Cancer Cells

Abstract

Breast cancer is a prevalent malignancy among women, posing significant public health challenges globally. Nuclear factor kappa B (NF-κB) pathway is implicated in breast cancer development and progression. This study aims to achieve the comprehensive chemical synthesis of oxazine derivatives and evaluate their potential as anticancer agents. Additionally, it involves conducting in silico analysis to assess the interaction of these compounds with the NF-κB pathway in human breast cancer cells. Oxazine derivatives were synthesized and evaluated for their anticancer activity against MCF-7 cells by cell viability assays. To determine the mass of the synthesized molecules, mass spectrometer was used. Additionally, ¹H and ¹³C NMR spectra were acquired using mass spectometry and NMR study. In silico analysis was conducted to assess the binding affinity of these compounds towards human NF-κB protein (1IKN). Among the synthesized compounds, oxazine derivative 6a demonstrated the highest potency with an IC₅₀ of 13.22 µM against MCF-7 cells. In silico analysis revealed that all synthesized compounds exhibited favorable binding energies towards the human NF-κB protein (1IKN). Oxazine derivatives, exemplified by compound 6a, show significant promise as effective agents against breast cancer cells, notably through NF-κB inhibition. The integration of computational methods in drug discovery describes their utility in optimizing compound design and understanding molecular interactions.