Dihydrochalcones: Methods of Acquisition and Pharmacological Properties-A First Systematic Review

Abstract

Dihydrochalcones are a class of secondary metabolites, for which demand in biological and pharmacological applications is still growing. They posses several healthendorsing properties and, therefore, are promising candidates for further research and development. However, low content of dihydrochalcones in plants along with their low solubility and bioavailability restrict the development of these compounds as clinical therapeutics. Therefore, chemomicrobial and enzymatic modifications are required to expand their application. This review aims at analyzing and summarizing the methods of obtaining dihydrochalcones and of presenting their pharmacological actions that have been described in the literature to support potential future development of this group of compounds as novel therapeutic drugs. We have also performed an evaluation of the available literature on beneficial effects of dihydrochalcones with potent antioxidant activity and multifactorial pharmacological effects, including antidiabetic, antitumor, lipometabolism regulating, antioxidant, antiinflammatory, antibacterial, antiviral, and immunomodulatory ones. In addition, we provide useful information on their properties, sources, and usefulness in medicinal chemistry.

Keywords: antioxidants; dihydrochalcones; microbial transformations; phloretin; sweeteners.

Figure 1

Dihydrochalcones from natural sources.

Scheme 1

Degradation pathway of neohesperidin dihydrochalcone by human intestinal microbiota [65].

Scheme 2

COMT-catalysed formation of two isomeric forms of O-methylated aspalathin metabolites.

Scheme 3

Bioreduction of chalcone (13) using variousmicroorganisms [69,70].

Scheme 4

Biohydrogenation of chalcones (16–23) catalyzed by S. cerevisiae [70].

Scheme 5

Bioreduction of chalcones in an ethanol–water system [71].

Scheme 6

Pathways of quercetin (26), apigenin (30), and luteolin (31) degradation by C. orbiscindens [73].

Scheme 7

Biotransformation of flavanone (35) catalyzed by selected bacteria and fungi [74].

Scheme 8

Chemoselective hydrogenation of 2′-hydroxychalcones (38, 42–48) by P. raistrickii [75].

Scheme 9

Reaction sequence proposed for the chemoselectve reduction of C=C of 2′-hydroxychalcone (38) mediated by ene-reductases [75].

Scheme 10

Biotransformation of chalcones (49 and 51) by Rhodotorula strains [76].

Scheme 11

Biotransformation of 2-hydroxychalcone (54) by cyanobaceria [78].

Scheme 12

Biotransformation of chalcones using select biocatalysts [69,79,80].