Molecular docking and synthesis of novel quinazoline analogues as inhibitors of transcription factors NF-κB activation and their anti-cancer activities.

NF-kB is a transcription factor protein complex that can be found in almost all animal cell types and is a key player in some cancers and inflammatory responses. It can enhance the proliferation rate, reduce apoptosis, as well as creating more blood flow to ensure the survival of cancer, thus blocking the NF-kB pathway has potential therapeutic benefit. We designed a series of compounds based on a quinazoline scaffold pharmacophore model which may have high binding affinity with the p50 subunit of NF-kB. The compound series with phenyl substitution at the 2 position of the quinazoline proved to be more effective at inhibiting NF-kB function both theoretically and experimentally. These compounds also reduce the proliferation of numerous tumor cell lines and the mean GI(50) for compound 2a is 2.88 μM against the NCI-60 cell line. At the same time, compound 2a can induce significant apoptosis in EKVX cell line at the concentration of 1 μM.