Centrally Acting Chalcones: From Anticancer and Antinociceptive Properties to Molecular Considerations

This review covers centrally acting chalcones while focusing on their anticancer and antinociceptive activities.

Identification of chalcones and their core scaffold with remarkable CNS activities has led to the screening of chalcone derivatives with promising effects against CNS types of cancer. The need for brain cancer and pain management that improve patient’s quality of life has continued to drive the search for new therapeutic approaches. Multitargeted molecules could offer relief against cancer with devastating pain.

This review reveals multiple targets of chalcones and provides structure-to-activity relationships and the mechanism of actions of chalcones. Research data consistently provide anticancer and antinociceptive evidence for some chalcones. The physicochemical characterization and molecular modeling of cardamonin—CD (multitargeted nutraceutical) with anticancer and antinociceptive properties provide insight into its pharmacological profile. Active sites of CD that are favorable for electrophilic attacks could interfere with cell proliferation pathways or trigger programmed cell death. The ability of oxygen atoms from CD to donate electrons may favor interaction with specific sites on cancer cells before a potential inhibition of uncontrolled cell growth and elicit an antinociceptive effect and antioxidant reactions that decrease inflammation and pain perception. Further research on chemical modifications and significant structural motifs of the privileged chalcone scaffold could produce new chalcone derivatives with enriched pharmacology.