**1. Introduction**

The NF-κB family of transcription factors plays crucial roles in cellular proliferation, survival, and immune responses. These consist of five members, including c-Rel, p65/RelA, RelB, p50/NF-κB1, and p52/NF-κB2 [1]. The most abundant form is a p65/RelA and p50/NF-κB1. In resting cells, NF-κB dimers remain in an inactive form in the cytoplasm during their association with an inhibitor of κB (IκB) [2]. Upon cellular activation by extracellular stimuli, the upstream IκB kinase (IKK) complex consisting of IKKα, IKKβ, and IKKγ phosphorylates IκB to degrade IκB, allowing the activation of NF-κB [3]. The activated NF-κB complex immediately translocates to the nucleus, thereby regulating the expression of many genes involved in cell survival, cell cycle progression, angiogenesis, invasion, and metastasis [4]. Tumor necrosis factor α (TNFα) is a potent pro-inflammatory cytokine that promotes tumor progression in most types of malignant tumors [5]. It stimulates NF-κB through the activation of IKK [6]. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the main streams of computer-aided drug design. Integrated drug design methods have been new trends in this area by combining information from both the ligand and the proteins [7,8]. For the integrated computer-aided studies, three-dimensional molecular structures of proteins and small molecules are prerequisites. Since the three-dimensional x ray structures of the IKKβ protein were revealed [9,10], the development of various inhibitors has been investigated and many inhibitors are commercially available [11–21]. However, it is uncommon for flavonoid compounds to be studied as IKKβ inhibitors [22,23]. Since flavonoids are second metabolites with phytoalexin properties and present in excess amount in plants, many studies and developments have been achieved as dietary supplements [24,25]. Flavonoids have also been reported to exhibit a variety of physiological activities and have been used in the development of a wide range of pharmaceuticals [26–28]. Chalcones, flavones, flavonols and isoflavones are diverse forms of flavonoids. In light of our research results, each form of flavonoid has been found to represent unique biological activities [29–33]. In this study, it was intended to investigate the anticancer activity through the IKKβ inhibitory effect after synthesizing the isoflavone compound **5** and revealing its solid-state structure by single crystal x-ray diffraction.
