Bioactive Natural and Synthetic Chalcones: Brazil as a Research Powerhouse in Discovery and Innovation

Abstract

Chalcones (1,3‐diphenyl‐2‐propen‐1‐one) are open‐chain flavonoids recognized for their structural diversity and broad pharmacological activities. Electrophilic α,β‐unsaturated carbonyl systems and versatile substitution patterns on aromatic rings have positioned the chalcones as privileged structures in medicinal chemistry. This review highlights the contributions of Brazilian investigations to the advances of chemistry and bioactivity of natural and synthetic chalcones over the last 40 years. A systematic search of PubMed, Scopus, Embase, and Web of Science up to February 2026 identified 661 publications, revealing a growing interest since the early 2000s and reflecting the consolidation of chalcone as a central subject of research groups. Brazilian investigations have shown chalcones as antibacterial, antifungal, antiparasitic, anticancer, and anti‐inflammatory agents, affording pivotal insights into structure–activity relationships and mechanisms of action at the molecular level. In addition, we submitted the most active chalcones to in silico evaluations, using SwissADME web tool, allowing a comparative analysis of their physicochemical, pharmacokinetics, and drug‐likeness properties. The results indicated the majority of these compounds demonstrated an appropriate drug‐like behavior. Collectively, the set of findings has positioned Brazil as an important research powerhouse of chemistry and pharmacology of chalcone and its derivatives, which may impact the discovery of innovative therapeutic agents.