Chiral Flavonoids as Antitumor Agents

Abstract

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.

Stereoselective Synthesis of Flavonoids: A Brief Overview

“…Due to their biological activities and current concernment in attaining enantiomerically pure forms, chiral flavonoids are gaining attention in the scientific field [ 66 ]. The isolation of these natural compounds can be time-consuming and associated with a low yield, which accentuate even more the demand for the synthesis of enantiomerically pure forms of them [ 67 ].…”

Flavonoids in Treatment of Chronic Kidney Disease

“…Among others, flavonoids stand out for being widely distributed in fruits, vegetables, grains, herbs, and beverages [ 49 ]. There are now more than 8000 varieties of flavonoids that have been structurally identified with a wide variety of biological properties [ 50 ]. Flavonoids are polyphenolic compounds synthesized in plants and as bioactive secondary metabolites.…”

“…The A-ring and B-ring are linked through a three-carbon bridge that usually arises as an oxygenated heterocyclic ring named C [ 51 ] ( Figure 1 ). Based on the degree of saturation and the level of oxidation of the C-ring, and different connections between the B-ring and C-ring, flavonoids can be classified into different groups, such as flavones (e.g., apigenin, rutin, and luteolin), flavonols (e.g., quercetin, kaempferol, myricetin, and fisetin), flavanol (e.g., epigallocathechin), isoflavonoids (e.g., genistein and daidzein), flavanones (e.g., naringin, naringenin, and hesperidin), and anthocyanidins (e.g., apigenidin, cyanidin, and malvidin) [ 18 , 50 ]. In recent years, flavonoids have attracted people’s attention.…”

Global regulatory factor FsveA up-regulate the production of antitumor substance in endophytic Fusarium solani

“…Also discovered were nucleosides (Zenchenko et al 2021), terpenes (de Vasconcelos Cerqueira Braz et al 2020, avonoids (Pinto et al 2021), phenols (Xia et al 2021), indole derivatives (Han et al 2020), and other compounds with potential antitumor activity. Furthermore, the metabolites were found to be signi cantly enriched in ABC transporter, purine metabolism, phenylalanine metabolism, 2-oxocarboxylic acid metabolism, aminoacyl-tRNA biosynthesis, and indole-like alkaloid metabolism via KEGG pathway enrich-ment analysis (Fig.…”