Flavonoids are a group of natural products with a great structural diversity, widely distributed in plant kingdom. They play an important role in plant growth, development and defense against aggressors. Flavonoids show a huge variety of biological activities such as antioxidant, anti-inflammatory, anti-mutagenic, antimicrobial and antitumor, being able to modulate a large diversity of cellular enzymatic activities. Among natural flavonoids, some classes comprise chiral molecules including flavanones, flavan-3-ols, isoflavanones, and rotenoids, which have one or more stereogenic centers. Interestingly, in some cases, individual compounds of enantiomeric pairs have shown different antitumor activity. In nature, these compounds are mainly biosynthesized as pure enantiomers. Nevertheless, they are often isolated as racemates, being necessary to carry out their chiral separation to perform enantioselectivity studies. Synthetic chiral flavonoids with promising antitumor activity have also been obtained using diverse synthetic approaches. In fact, several new chiral bioactive flavonoids have been synthesized by enantioselective synthesis. Particularly, flavopiridol was the first cyclin-dependent kinase (CDK) inhibitor which entered clinical trials. The chiral pool approaches using amino acid as chiral building blocks have also been reported to achieve small libraries of chrysin derivatives with more potent in vitro growth inhibitory effect than chrysin, reinforcing the importance of the introduction of chiral moieties to improve antitumor activity. In this work, a literature review of natural and synthetic chiral flavonoids with antitumor activity is reported for the first time.

There is a drive within the cosmetic industry towards the development of more sustainable products, supported by consumer awareness of the environmental footprint. The cosmetic industry is rising to meet consumer demand by following practices, such as the use of by-products from agro-industrial waste. Quercus suber is a tree prevalent in the Mediterranean basin. The extraction of cork is considered sustainable, as this process does not harm the tree, and the amount of cork produced increases with the number of extractions. Beyond this, the cork industry produces by-products that are used to sustain the industry itself, such as cork powder, which is reused for generating energy. Additionally, cork and cork by-products contain bioactive compounds mainly with antioxidant activity that can be of use to the cosmetic industry, such as for antiaging, anti-acne, anti-inflammatory, and depigmenting cosmetic products. We provide the reader with an overview of the putative cosmetic applications of cork and its by-products as well as of their bioactive compounds. It is noteworthy that only a few cork-based cosmetic products have reached the market, namely antiaging and exfoliant products. Clearly, the use of cork upcycled cosmetic ingredients will evolve in the future considering the wide array of biological activities already reported.

Nature represents a rich source of bioactive compounds, with flavones emerging as privileged scaffolds owing to their multiple biological activities. Their antitumor potential arises from their ability to modulate pathways implicated in cancer progression and multidrug resistance, but structural modifications are often required to improve their pharmacokinetic properties and target selectivity. Incorporating chiral moieties, such as amino acids, may improve their potency and selectivity. Herein, we report the stereoselective synthesis of 32 new chiral derivatives of flavones (CDFs) obtained by coupling four commercial flavones with the enantiomerically pure amino esters and amino acids of tryptophan and tyrosine. Overall, the amino ester derivatives showed greater antiproliferative activity than their parent flavones against four cancer cell lines. 6HF‐DTrp ( 14 ) and 7HF‐DTrp ( 18 ) demonstrated micromolar equipotent inhibition with IC50 <21 µM against all cell lines. Most CDFs preferentially affected cancer cells over nontumor HPAEpiC cells, particularly 7HF‐DTrp ( 18 ), which displayed selectivity indices above 6. Metabolic assays exposed heterogeneous effects on glucose consumption and lactate production, suggesting that CDF‐induced cytotoxicity depends on the metabolic flexibility of each tumor phenotype rather than a universal mechanism. Furthermore, in vitro and in silico studies suggest potential P‐glycoprotein (P‐gp) inhibitory activity for 6HF‐DTrp ( 14 ) and 7HF‐DTrp ( 18 ).