Preparation of Retinoyl-Flavonolignan Hybrids and Their Antioxidant Properties

Abstract

Antioxidants protect the structural and functional components in organisms against oxidative stress. Most antioxidants are of plant origin as the plants are permanently exposed to oxidative stress (UV radiation, photosynthetic reactions). Both carotenoids and flavonoids are prominent antioxidant and anti-radical agents often occurring together in the plant tissues and acting in lipophilic and hydrophilic milieu, respectively. They are complementary in their anti-radical activity. This study describes the synthesis of a series of hybrid ester conjugates of retinoic acid with various flavonolignans, such as silybin, 2,3-dehydrosilybin and isosilybin. Antioxidant/anti-radical activities and bio-physical properties of novel covalent carotenoid-flavonoid hybrids, as well as various mixtures of the respective parent components, were investigated. Retinoyl conjugates with silybin—which is the most important flavonolignan in silymarin complex—(and its pure diastereomers) displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than both the parent compounds and their equimolar mixtures.

Study on the Synthesis, Antioxidant Properties, and Self-Assembly of Carotenoid–Flavonoid Conjugates

“…A similar DCC or EDC/DMAP esterification method was applied for the synthesis of retinoate esters of various flavonolignans in low yields. The prepared esters showed increased radical scavenging activity [26].…”

“…Interestingly, the antioxidant activity of daidzein increased while that of quercetin decreased after derivatization [25].A similar DCC or EDC/DMAP esterification method was applied for the synthesis of retinoate esters of various flavonolignans in low yields. The prepared esters showed increased radical scavenging activity [26].Here, we present a straightforward method for the regioselective covalent coupling of daidzein and chrysin with various carotenoids through a long spacer, which ensures flexibility and allows the hydrophilic and lipophilic moieties to move away or draw closer. Three different types of carotenoids were studied, the C 30 primary alcohol 8 -apo-β-carotenol, the symmetric secondary diol zeaxanthin, and Molecules 2020, 25, 636 3 of 21 the asymmetric κ-carotenoid capsanthin.…”

Phosphodiester Silybin Dimers Powerful Radical Scavengers: A Antiproliferative Activity on Different Cancer Cell Lines

“…Dimers, obtained as mixture of diastereoisomers, were very soluble in water and stable in both human serum and alkaline phosphatase. Despite silibinin ( 1ab ) and silybins ( 1a and 1b ) [ 17 , 18 ] not having strong antioxidant activity, dimers 9′′-9′′ showed a strong radical-scavenging ability. In particular, the ability to scavenge 1 O 2 in H 2 O was tested, and a higher reactivity towards HO ● (about two times) was estimated for the 3-9′′ and 9′′-9′′ dimers with respect to silibinin.…”

Cold-Active Lipase-Based Biocatalysts for Silymarin Valorization through Biocatalytic Acylation of Silybin

“…In order to obtain phosphorylated conjugates, Zarelli et al initially acetylated silybin in a complex three-step organic synthetic process with a 75% yield [15]. Moreover, there are encapsulated silymarin variants in matrices less toxic and much better accepted by the human organism [10,16]. Silymarin could be included in natural β-cyclodextrins forming complexes, often used because of their solubilization potential within the body barriers without metabolic degradation [14].…”