Drug-resistant bacteria constitute a big barrier against current pharmacotherapy. Efforts are urgent to discover antibacterial drugs with novel chemical and biological features. Our work aimed at the synthesis, evaluation of antibacterial effects, and toxicity of licochalcone C (LCC), a naturally occurring chalcone. The synthetic route included six steps, affording a 10% overall yield. LCC showed effects against Gram-positive bacteria (MIC = 6.2–50.0 µg/mL), Mycobacterium species (MIC = 36.2–125 µg/mL), and Helicobacter pylori (MIC = 25 µg/mL). LCC inhibited the biofilm formation of MSSA and MRSA, demonstrating MBIC₅₀ values of 6.25 μg/mL for both strains. The investigations by fluorescence microscopy, using PI and SYTO9 as fluorophores, indicated that LCC was able to disrupt the S. aureus membrane, similarly to nisin. Systemic toxicity assays using Galleria mellonella larvae showed that LCC was not lethal at 100 µg/mL after 80 h treatment. These data suggest new uses for LCC as a compound with potential applications in antibacterial drug discovery and medical device coating.

Efforts to develop weed management alternatives are urgently required due to various challenges, such as declining crop yields, rising production costs, and the growing prevalence of herbicide-resistant weed species. Chalcones occur in nature and have phytotoxic potential and concise synthesis; additionally, they are multifunctional, with diverse biomolecular targets and a broad spectrum of biological activities. This study sought to assess the herbicidal potential of 3?-hydroxychalcones against weed species under laboratory conditions. Their effects were investigated using germination bioassays, early growth measurements, and the seedling vigor index, all prepared with a concentration of 1 × 10^?3 mol L^?1 3?-hydroxychalcones. 3?-Hydroxy-4-pyridyl-chalcone caused the greatest inhibition (81%) of the seedling length in Urochloa decumbens. Other 3?-hydroxychalcones also caused large initial growth reductions, such as 3?-hydroxy-4-pyridyl-chalcone (75%) and 3?-hydroxy-4-nitrochalcone (68%) in Digitaria insularis and 3?-hydroxy-4-bromochalcone (73%) in Raphanus raphanistrum. The greatest reduction in the seedling vigor index was 81% in D. insularis treated with the 3?-hydroxy-4-bromochalcone. The same 3?-hydroxychalcone caused an 80% reduction in Amaranthus viridis. In conclusion, 3?-hydroxychalcones exhibit herbicidal activity, suggesting they could serve as a solution for future weed management strategies.

Chalcones are naturally occurring open-chain flavonoids widely distributed in plants and recognized for their broad spectrum of pharmacological activities. Their versatile scaffold allows for extensive structural modifications, leading to a diverse range of natural and synthetic derivatives with notable biological potential. In the context of viral infections, chalcones have demonstrated remarkable efficacy against a variety of human pathogens, including dengue virus, HIV, HCV, influenza A, SARS-CoV-2, and other emerging viruses. Beyond human health, several chalcones have shown potent activity against plant viruses such as tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV), and animal viruses including porcine reproductive and respiratory syndrome virus (PRRSV) and mammalian reovirus (MRV), underscoring their broad antiviral spectrum. These compounds act through multiple mechanisms, including the inhibition of viral enzymes (e.g., proteases, polymerases, and integrases), interference with viral entry and replication, and the modulation of host-related pathways. Recent advances in molecular docking, structure–activity relationship (SAR) studies, and synthetic optimization have further highlighted chalcones as a promising scaffold for antiviral drug discovery. Accordingly, this review summarizes and categorizes antiviral chalcones reported over the last two decades, emphasizing and critically discussing their molecular targets, mechanisms of action, and pharmacological potential as lead compounds. It also provides a comparative perspective on their pharmacological relevance by correlating their activities against standard therapeutic agents and reference inhibitors. Furthermore, the most recurrent viral targets were critically discussed regarding their conservation, expected genetic barriers to resistance, and the global SAR trends identified for the corresponding antiviral chalcones. Finally, in silico ADMET profiling of the most promising naturally occurring chalcones was performed to evaluate their drug-likeness and pharmacokinetic properties, offering guidance for future structural optimization and translational development. Collectively, these findings highlight the chalcone scaffold as a versatile platform for the development of novel antiviral agents targeting diverse viral and host pathways.