Chalcones and Flavanones Bearing Hydroxyl and/or Methoxyl Groups: Synthesis and Biological Assessments

Abstract

Chalcones and flavanones are isomeric structures and also classes of natural products, belonging to the flavonoid family. Moreover, their wide range of biological activities makes them key scaffolds for the synthesis of new and more efficient drugs. In this work, the synthesis of hydroxy and/or methoxychalcones was studied using less common bases, such as sodium hydride (NaH) and lithium bis(trimethylsilyl)amide (LiHMDS), in the aldol condensation. The results show that the use of NaH was more effective for the synthesis of 2 -hydroxychalcone derivatives, while LiHMDS led to the synthesis of polyhydroxylated chalcones in a one-pot process. During this study, it was also possible to establish the conditions that favor their isomerization into flavanones, allowing at the same time the synthesis of hydroxy and/or methoxyflavanones. The chalcones and flavanones obtained were evaluated to disclose their antioxidant, anticholinesterasic, antibacterial and antitumor activities. 2 ,4 ,4-Trihydroxychalcone was the most active compound in terms of antioxidant, anti-butyrylcholinesterase (IC 50 26.55 ± 0.55 µg/mL, similar to control drug donepezil, IC 50 28.94 ± 1.76 µg/mL) and antimicrobial activity. 4 ,7-Dihydroxyflavanone presented dual inhibition, that is, the ability to inhibit both cholinesterases. 4 -Hydroxy-5,7-dimethoxyflavanone and 2 -hydroxy-4-methoxychalcone were the compounds with the best antitumor activity. The substitution pattern and the biological assay results allowed the establishment of some structure/activity relationships.

Identification of Chalcone Derivatives as Inhibitors of Leishmania infantum Arginase and Promising Antileishmanial Agents

“…Chalcones, or 1,3-diaryl-2-propen-1-ones, are naturally occurring compounds belonging to the flavonoid family. They are characterized by a simple scaffold of two phenolic rings connected by a three-carbon α,β unsaturated carbonyl bridge (Rosa et al, 2019 ). Compounds with chalcone structures exhibit diverse biological activities and, consequently, they have attracted researchers' attention as a curious starting point for the synthesis of molecular entities with potential pharmacological properties (Gomes et al, 2017b ).…”

Natural Compounds: A Dynamic Field of Applications

“…Since they are chemically very labile, chalcones and flavanones are also excellent scaffolds to medicinal chemistry and development of new drugs [64][65][66]. In this context, the optimization of the aldol condensation synthesis route by using unexplored bases to prepare hydroxylated and methoxylated chalcones and flavanones proposed by Rosa et al [67] is well come. The application of the synthesized compounds as cytotoxic, antioxidant, antibacterial and anticholinesterase agents were evaluated, and SAR are discussed.…”

Synthesis Chalones and Their Isomerization into Flavanones and Azaflavanones

“…The yields are usually very good and the reaction occurs at room temperature. Depending on the substitution pattern and the solvent/base system used, the reaction time varies from 3 to 20 h [1,11,12]. The system of methanol/NaOH is not suitable for the synthesis of nitro-derivatives nor for the synthesis of 2’-aminochalcones.…”

“…Chalcones are naturally occurring compounds, more recognized as the precursors of other flavonoids, but both natural and synthetic derivatives present interesting biological activities [1]. Furthermore, their synthesis is also investigated due to their use in the synthesis of other biologically important compounds, the flavanones and 2-aryl-2,3-dihydroquinolin-4(1 H )-ones.…”