Chalcones are α,β-unsaturated ketones, naturally produced as flavonoids and isoflavonoids precursors. Their privileged chemical structure enables their conjugation with different groups, aiming to improve their chemical properties and biological activities. Chalcone-sulfonamide hybrids display a range of biological activities and have been widely investigated for their anticancer potential, being considered promising molecules for cancer treatment. This systematic review aimed to summarize the information available in the literature about the anticancer potential of chalcones-sulfonamides in vitro and in vivo and their mechanisms of action. An electronic search was performed across scientific databases (PubMed, Web of Science, Emabase, and Scopus), and two blinded authors selected the studies according to the inclusion and exclusion criteria. The search yielded 1,467 articles, of which 18 were considered eligible for the review. Our analysis demonstrated that chalcones-sulfonamides are mainly obtained by Claisen-Schmidt condensation and can receive several functional groups, directly affecting their activity. Chemical substitutions often involve the addition of methoxy or chlorine groups at different positions of the molecule. Chalcones-sulfonamides demonstrated relevant cytotoxic potential in vitro and reduced tumor growth in vivo. The mechanisms underlying these effects involve oxidative stress, increased intracellular Reactive Oxygen Species (ROS), and DNA damage. The oxidative stress induced by chalcones-sulfonamides also seems to contribute to the inhibition of Carbonic Anhydrase, which is frequently overexpressed in cancer cells. Altogether, chalcones-sulfonamides may lead to cell death by different pathways, predominantly via apoptosis or necroptosis.
