Chalcone derivatives are considered valuable species because they possess a ketoethylenic moiety, CO–CH=CH–. Due to the presence of a reactive α,β-unsaturated carbonyl group, chalcones and their derivatives possess a wide spectrum of antiproliferative, antifungal, antibacterial, antiviral, antileishmanial, and antimalarial pharmacological properties. Recent developments in heterocyclic chemistry have led to the synthesis of chalcone derivatives, which had been biologically investigated toward certain disease targets. The major aspect of this review is to present the most recent synthesis of chalcones bearing N, O, and/or S heterocycles, revealing their biological potential during the past decade (2010–2021). Based on a review of the literature, many chalcone–heterocycle hybrids appear to exhibit promise as future drug candidates owing to their similar or superior activities compared to those of the standards. Thus, this review may prove to be beneficial for the development and design of new potent therapeutic drugs based on previously developed strategies.

Background & Objectives: Heterocyclic pyrimidine and pyrazole rings have attracted the interest of medicinal chemists because of their pharmacological potential including antimicrobial activity. Based on molecular hybridization, new chalcones 6a-g and pyrimidines 7a-g based on a pyrazole scaffold were designed. Methods: The synthesis of these compounds involved mild condensation reactions between compound 4 and various aromatic aldehydes in a mixture of ethanol/NaOH (95:5 v/v) to give the corresponding chalcones 6a-g. These chalcones were further reacted with urea in the presence of a base in ethanol to produce the pyrimidine derivatives 7a-g. These new candidates were screened for their in vitro antimicrobial activities and molecular docking studies were evaluated. Results: The antibacterial and antifungal studies of all synthesized compounds against the strains tested showed that compounds 6c, d, and 7c, d exhibited the highest antibacterial and antifungal activities. In addition, the structure-activity relationship and docking studies are discussed. Conclusion: The synthesized compounds 6c, 6d, 7c, and 7d showed the highest antibacterial and antifungal activities against the tested strains.