Leixiang Yang

Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage

An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a-e and 4a-j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, rat liver homogenate lipid peroxidation inhibition, PC12 cells protection from oxidative damage, and xanthine oxidase inhibition. These dihydroflavonols displayed positive quenching abilities towards O(2)(-) and DPPH free radicals, in which the majority exhibited superior antioxidant properties to Vitamin C. cis-Configurated compound (+/-)-3e demonstrated remarkable inhibition to LPO with an IC(50) value of 1.9+/-0.3 microM, which was apparently stronger than that of quercetin (IC(50)=6.0+/-0.4 microM). trans-Configurated dihydroflavonol (+/-)-4h exhibited significant protective effect on PC12 cells against oxidative damage with an EC(50) value of 41.5+/-5.3 microM, more effective compared to that of quercetin (EC(50)=81.8+/-8.7 microM). The 6-OH-5,7-dimethoxy analogue (+/-)-3d showed significant inhibition of xanthine oxidase with an IC(50) value of 16.0+/-0.8 microM, which is superior to that of allopurinol (IC(50)=23.5+/-2.0 microM). In addition to the hypothesized action mechanism of the bio-active compounds, 3D modeling was used to analyze the relationship between the minimized-energy structures and antioxidant activities.

Preparation of C-23 esterified silybin derivatives and evaluation of their lipid peroxidation inhibitory and DNA protective properties

A diverse series of C-23 esterified silybin derivatives (1a-n) were designed and synthesized. The antioxidative properties of these compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging, ferrous ion chelation, and inhibition of rat liver homogenate lipid peroxidation. Their protective effects on the prevention of hydrogen peroxide induced DNA damage were also investigated. Most of the synthesized compounds exhibited more effective antioxidant activities than silybin. The esterified silybin analogues displayed satisfactory performance especially on iron chelation and antiperoxidative activity. Compound 1n in particular exhibited remarkable antiperoxidative effect with an IC(50) value of 0.2+/-0.1 microM, which was stronger than that of quercetin (IC(50)=1.8+/-0.6 microM). Compounds 1c, 1e, 1g, 1h and 1k displayed potent, dose-dependent protective properties against DNA cleavage. The results of the bioassays support the antioxidative and DNA protective effects of these synthesized silybin derivatives.

Synthesis and antioxidant evaluation of novel silybin analogues

In this work, we evaluated the antioxidant properties of the eight novel silybin analogues for their capacity to scavenge free radicals including superoxide anion radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in vitro. Compound 7d demonstrated an excellent antioxidant effect in scavenging superoxide anion free radical with an IC50 value of 26.5 μM, while the IC50 of quercetin (the reference compound) was 38.1 μM. Compounds 7b, 7e, 7h showed certain scavenging activities for both types of free radicals.

Preparation of ferulic acid derivatives and evaluation of their xanthine oxidase inhibition activity

Several ferulic acid ethyl esters (3a–h) were synthesized under the Knoevengel reaction condition and they were further reduced to afford the respective allylic alcohol derivatives (4a–g). Some of them were evaluated for the xanthine oxidase (XO) inhibitory activity. Among them, 3h exhibited a significant inhibitory activity with an IC50 value of 1.35 × 10−5 M, while the IC50 value of allopurinol used as the positive control was 1.49 × 10−5 M. The study suggested that the higher acidity of the phenolic OH group in the ferulic acid derivatives might result in improved XO inhibitory activity.

Synthesis and structure–activity relationship studies of cytotoxic cinnamic alcohol derivatives

Three series of di- and trisubstituted derivatives of cinnamic alcohol and its conjugated dienol analogues were designed and synthesised. The derivatives were screened for cytotoxicity against nine tumour cell lines: KB, A549, Hela, CNE, PC-3, BEL-7404, HL-60, BGC823 and P388D1. Most of the cinnamic alcohol derivatives showed cytotoxic activity. The compound 7-(4′,5′-dichlorobenzyloxy)-6,8-dihydroxycinnamic alcohol (55) exhibited significant cytotoxicity to seven human tumour cell lines on a micromolar range, especially with regard to the KB and P388D1 cell lines, showing IC50 values of 0.4 and 0.5 µM, respectively. The structure–activity relationships of the derivatives are discussed.

Total synthesis and cytotoxicity evaluation of syrinenin-4-O-farnesylether and its analogues

First synthesis of natural product, syrinenin-4-O-farnesylether (1), was carried out via two different paths. Four of its derivatives (9–12) were also prepared. Cytotoxicity screening of the selected compounds were performed on six tumour cell lines. Compound 12 exhibited prominent IC50 values of 1.9 μM and 0.8 μM on CNE and PC-3 cells, respectively.