Schiff Base Moiety Could be a Possible Inhibitor of Mutated Nrf2/KEAP1 Associated Cancer

Abstract

In recent studies, the cap’n’collar (CNC) bZIP transcription factor Nrf2 plays a pivotal role in cancer drug development. The Nrf2/KEAP1 pathway is the most important signalling cascade involved in the resistance of oxidative damage induced by external chemicals. The Nrf2 maintains cellular homeostasis, anti-inflammatory, and anticancer properties by activating downstream signalling pathways and their cell survival. But, a recent literature survey suggested that mutated KEAP1/Nrf2 is responsible for cancer formation by suppressing apoptosis and metabolic reprogramming. More importantly, Nrf2 is proven to contribute to the chemoresistance and radioresistance of cancer cells as well as inflammation-induced carcinogenesis. A number of Nrf2 inhibitors, particularly Schiff base molecules discovered for cancer treatment, were reviewed in this chapter. Schiff bases or azomethines are compounds formed by a condensation reaction between primary amines and aldehydes, and have various biological, medicinal, clinical, pharmacological and analytical applications. These provide a new strategy that targeting Nrf2 could be a promising therapeutic approach against cancer. This review emphasises the role of Schiff base to summarise the effects of Nrf2 in cancer, revealing its function both in cancer prevention and inhibition, to further synthesise the novel Schiff base-related anticancer treatment.