Chalcones are compounds containing an α,β-unsaturated carbonyl group that have been studied due to their structural simplicity, ease of synthesis, and broad spectrum of biological activities. Within this family, nitrochalcones have gained relevance due to the influence of the nitro group (–NO₂) on the modulation of their electronic properties, chemical reactivity, and pharmacological behavior. This review presents a critical analysis of advances in the biological activities and possible mechanisms of action of nitrochalcones and their derivatives, with an emphasis on their structure–activity relationships and therapeutic potential. The available evidence shows that nitrochalcones and their derivatives act as multitarget molecules, capable of intervening in key biological processes such as oxidative stress, mitochondrial dysfunction, inflammation, and cell signaling pathways associated with proliferation and apoptosis. Several studies report anticancer, anti-inflammatory, antiparasitic, antimicrobial, antifungal, and cardiovascular activities, often with favorable selectivity toward pathological cells over healthy cells.

Fluorinated chalcones are molecules reported to possess potent anticancer properties against triple-negative breast cancer (TNBC) cells. However, their molecular mechanisms have not yet been fully explored. Using bioinformatics tools, we analyzed the transcriptomes of MDA-MB-231 cells treated with either a novel fluorinated chalcone (compound 3) or a control in order to identify differentially expressed (DE) genes associated with its anticancer activity and determine the biological processes in which these genes are involved. A fluorinated chalcone was synthesized using the Claisen–Schmidt method. The transcriptome of MDA-MB-231 cells was then analyzed on an Illumina NextSeq500, and DE genes with significant changes in expression were identified using the DESeq2 v1.38.0 bioinformatics tool under the strict detection criteria of |log2FC| ≥ 2 and adjusted p < 0.05. We identified 504 DE genes, which were enriched in terms related to “regulation of cell death”, “cation transport”, “response to topologically incorrect proteins”, and “response to unfolded proteins”. Surprisingly, these genes were involved in “the HSF1-dependent transactivation pathway” and “the attenuation phase pathway”. This bioinformatics-based study suggests that the tested fluorinated chalcone could influence HSF-1 silencing in addition to promoting the up-regulation of several genes involved in stress-induced apoptosis. Therefore, the tested compound could have enormous potential as a novel approach for TNBC treatment.

Organic synthesis plays a fundamental role in medicinal chemistry, allowing the production of compounds with desirable pharmacological properties. In this context, new synthesis methods, such as the use of ultrasound, are continuously being explored to improve the efficiency and sustainability of these processes. In this work, the synthesis and structural characterization of 2-nitrochalcone derivatives substituted with electron-withdrawing (fluoro) and electron-donating (methoxy) groups in the three isomeric positions of the B ring via nuclear magnetic resonance and ultrasound are presented; both a conventional method and a nonconventional ultrasound-assisted method are used. The results show that both methodologies are effective for obtaining these compounds, but the conventional method presents some additional advantages in the case of these nitrochalcones, such as shorter reaction times and better reaction yields.

In this study, an alternative methodology for the aqueous synthesis of chalcones is presented. This methodology is ecologically sound, since it occurs at room temperature and utilizes only KOH (a green base). In addition, it showed a broad applicability, as evidenced by the preparation of 37 derivatives in good to excellent yields (up to 98%). Moreover, most compounds were recovered pure enough through straightforward fil-tration and water washing. The development of the reaction is accompanied by a study that demonstrates that the yield of the products and the reaction mechanism are directly affected by the solubility and physical state of the starting materials.

In this study, an alternative methodology for the aqueous synthesis of chalcones is presented. This procedure is performed on a green basis at room temperature (25–40 °C) and using KOH. From this method, thirty-seven derivatives were obtained with yields of up to 98%. In addition, many compounds were recovered sufficiently pure by direct filtration and washing with water. The manuscript is accompanied by a study that demonstrates that the yield of the products and the reaction mechanism, which occurs on-water and in-water, are directly affected by the solubility and physical state of the starting materials.

Natural products remain an important source of structurally diverse compounds for the discovery of new antimicrobial agents. Gliricidia sepium (Jacq.) Kunth ex Walp. is a medicinal species widely distributed in tropical regions and is recognized as a source of flavonoids, phenolic acids, coumarins, glycosides, and other specialized metabolites with diverse biological activities. Previous phytochemical investigations of this species have reported compounds such as oxytroside, o-coumaric acid, and melilotic acid, highlighting its potential as a source of bioactive natural products. In the present study, the influence of sequential solvent extraction on the recovery of antibacterial metabolites from G. sepium leaves was evaluated. Dried leaves were sequentially extracted by maceration with n-hexane, ethyl acetate, and methanol, and the resulting crude extracts were tested against Staphylococcus aureus using the agar disk diffusion assay at concentrations of 12.5, 25, 50, 100, and 200 μg/mL. Antibacterial activity varied according to solvent polarity and extract concentration. The methanolic extract exhibited the highest activity, producing an inhibition zone of 1.1 cm at 200 μg/mL, followed by the ethyl acetate extract (0.8 cm), whereas the hexane extract showed only slight activity (0.7 cm). The positive control produced inhibition zones ranging from 2.8 to 3.7 cm. These findings indicate that sequential solvent extraction influences the recovery of antibacterial constituents from G. sepium and support further bioactivity-guided fractionation and phytochemical characterization of the most active extracts.