Chalcones: Synthetic Chemistry Follows Where Nature Leads

Chalcones belong to the flavonoid class of phenolic compounds. They form one of the largest groups of bioactive natural products. The potential anticancer, anti-inflammatory, antimicrobial, antioxidant, and antiparasitic properties of naturally occurring chalcones, and their unique chemical structural features inspired the synthesis of numerous chalcone derivatives. In fact, structural features of chalcones are easy to construct from simple aromatic compounds, and it is convenient to perform structural modifications to generate functionalized chalcone derivatives. Many of these synthetic analogs were shown to possess similar bioactivities as their natural counterparts, but often with an enhanced potency and reduced toxicity. This review article aims to demonstrate how bioinspired synthesis of chalcone derivatives can potentially introduce a new chemical space for exploitation for new drug discovery, justifying the title of this article. However, the focus remains on critical appraisal of synthesized chalcones and their derivatives for their bioactivities, linking to their interactions at the biomolecular level where appropriate, and revealing their possible mechanisms of action.

Automated summary

Chalcones belong to the flavonoid class of phenolic compounds and possess potential anticancer, anti-inflammatory, antimicrobial, antioxidant, and antiparasitic properties. The synthesis of chalcone derivatives inspired by their unique chemical features has led to the discovery of compounds with similar bioactivities to natural chalcones but with enhanced potency and reduced toxicity. The focus is on evaluating the bioactivities of synthesized chalcones and their derivatives, as well as understanding their possible mechanisms of action at the biomolecular level.