Curzerene and curzerenone: two furanosesquiterpenoids of interest for cancer treatment and beyond

This is the authors' abstract. We don't add key points for this paper.

The two related sesquiterpenes curzerene and curzerenone have been found in many plants, notably in the rhizomes of Curcuma species and other Asian medicinal plants and essential oils. These two natural products, present in several traditional Chinese medicines, belong to a family of furanosesquiterpenoids which includes the less stable analogues furanodiene and furanodienone. Synthetic processes have been described to obtain curzere(no)ne and analogues such as epi - and pyro-curzerenone. An overview of the chemistry and pharmacology of these natural products is reported here. Curzere(no)ne display antioxidant and anti-inflammatory properties. They have shown modest but significant activities against distinct viruses, bacteria, and certain parasites, as well as insecticidal properties. They showed an interest also to limit hyperlipidemia and neuroinflammation. But the most promising point refers to their anticancer activities. Curzerenone combines three complementary properties: (i) inhibition of cancer cell survival and proliferation, (ii) reduction of tumor cell migration and invasion, (iii) promotion of T cell activation and proliferation, notably via a down-regulation of the PD-L1 checkpoint. These properties translate into a capacity of curzerenone to reduce markedly tumor growth in vivo. These considerations shall encourage the development of more potent and safer curzerenone derivatives. Small molecules capable of suppressing immune evasion of tumors are actively searched. Curzerenone represents an interesting scaffold, chemically accessible, to design novel regulators of the PD-1/PD-L1 checkpoint. The review highlights the interest for these two natural products in oncology and beyond.