Synthesis and antioxidant activity of hydroxylated phenanthrenes as cis-restricted resveratrol analogues

Ding, Dejun; Cao, Xiaoyan; Dai, Fang; Li, Xiu-Zhuang; Liu, Guoyun; Dong, Lin; Fu, Xing; Jin, Xiaoling; Zhou, Bo

doi:10.1016/j.foodchem.2012.05.074

Cited by 34 publications

(15 citation statements)

References 53 publications

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“…13 In contrast, impairment of the conjugated links, such as hydrogenation of the aliphatic double bond, could significantly decrease its electron‐donating ability, as exemplified by DHR and RES ( n =0.55 and 1.45, respectively). This is in agreement with our previous finding that extension by conjugation for the stilbene scaffold of RES is an efficient strategy to improve its antioxidant activity 5d,e,f…”

Section: Resultssupporting

confidence: 93%

Influence of Glucuronidation and Reduction Modifications of Resveratrol on its Biological Activities

Ding

Yan

et al. 2013

ChemBioChem

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Resveratrol (3,5,4'-trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced products. This begs the question of whether the metabolites of RES contribute to its in vivo biological activity. To explore this possibility, we synthesized its glucuronidation (3-GR and 4'-GR) and reduction (DHR) metabolites, and evaluated the effect of these structure modifications on biological activities, including binding ability with human serum albumin (HSA), antioxidant activity in homogeneous solutions and heterogeneous media, anti-inflammatory activity, and cytotoxicity against various cancer cell lines. We found that 1) 4'-GR, DHR and RES show nearly equal binding to HSA, mainly through hydrogen bonding, whereas 3-GR adopts a quite different orientation mode upon binding, thereby resulting in reduced ability; 2) 3-GR shows comparable (even equal) ability to RES in FRAP- and AAPH-induced DNA strand breakage assays; DHR, 3-GR, and 4'-GR exhibit anti-hemolysis activity comparable to that of RES; additionally, 3-GR and DHR retain some degree activity of the parent molecule in DPPH.-scavenging and cupric ion-initiated oxidation of LDL assays, respectively; 3) compared to RES, 4'-GR displays equipotent ability in the inhibition of COX-2, and DHR presents comparable activity in inhibiting NO production and growth of SMMC-7721 cells. Relative to RES, its glucuronidation and reduction metabolites showed equal, comparable, or some degree of activity in the above assays, depending on the specific compound and test model, which probably supports their roles in contributing to the in vivo biological activities of the parent molecule.

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Section: Resultssupporting

confidence: 93%

Influence of Glucuronidation and Reduction Modifications of Resveratrol on its Biological Activities

Ding

Yan

et al. 2013

ChemBioChem

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“…The key features for the antioxidant activity are highlighted in different colours: vanillin moiety (blue), phenolic functionality (yellow), tertiary amine (red) and electronic delocalisation (purple).M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTThe most interesting antioxidant compounds 1b and 2c showed their ability to protect plasmid DNA from radical damage with IC 50 values 3.6 and 0.6 µM, respectively. Compound 2c exhibited total DNA protection up to concentration of 4 µM, demonstrating improved activity compared with other synthetic compounds derived from natural occurring antioxidant resveratrol[30]. Interestingly a homologue compound of 2c reported by Lee et al[19] with a benzyl group linking the four vanillin moieties A (figure 4) instead of a phenyl group as in the case of 2c (0.6 µM) showed much weaker DNA protection activity at concentration > 45 µM.…”

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confidence: 85%

Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties

Scipioni

Kay

Megson³

et al. 2018

European Journal of Medicinal Chemistry

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Antioxidants have been the subject of intense research interest mainly due to their beneficial properties associated with human health and wellbeing. Phenolic molecules, such as naturally occurring Resveratrol and Vanillin, are well known for their anti-oxidant properties, providing a starting point for the development of new antioxidants. Here we report, for the first time, the synthesis of a number of new vanillin through the reductive amination reaction between vanillin and a selection of amines. All the compounds synthesised, exhibited strong antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c being the most active. The latter also demonstrated the ability to protect plasmid DNA from oxidative damage in the presence of the radical initiator AAPH. At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative damage (HO, 400 μM) with both 1b and 2c. The presence of a tertiary amino group, along with the number of vanillin moieties in the molecule contribute for the antioxidant activity. Furthermore, the delocalization of the electron pair of the nitrogen and the presence of an electron donating substituent to enhance the antioxidant properties of this new class of compounds. In our opinion, vanillin derivatives 1b and 2c described in this work can provide a viable platform for the development of antioxidant based therapeutics.

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“…19 Phenanthrene-derived synthetic and natural products have demonstrated a variety of pharmacological effects, such as cytotoxicity, phytotoxicity, and anti-inflammatory, antimicrobial, antioxidant, antiplatelet aggregation, and antiallergic activities. [20][21][22][23][24] These important findings laid the foundation for the design of new nano-sized self-assembled architectures with phenanthrene-derived donors and arene-Ru-based acceptors, with the expectation of improved biological results in comparison with available chemotherapeutic agents. Studies on similar complexes suggest that phenanthrene-derived donors and arene-Ru-based acceptors will work together in a synergistic manner as complementary building blocks; the phenanthrene unit will interact with DNA, whereas the ruthenium center will bind to proteins.…”

Section: Introductionmentioning

confidence: 97%

Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors

Kim¹,

Song

Singh

et al. 2015

IJN

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Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3, 6-bis(pyridin-3- ylethynyl) phenanthrene (bpep) ( 1 ) and one of the three dinuclear arene ruthenium clips, [(η 6 - p -iPrC 6 H 4 Me) 2 Ru 2 -(OO\OO)][OTf] 2 (OO\OO =2, 5-dioxido-1, 4-benzoquinonato, OTf = triflate) ( 2 ), 5, 8-dioxido-1, 4-naphthoquinonato ( 3 ), or 6, 11-dioxido-5, 12-naphthacenediona ( 4 ), resulted in three molecular bowls 5 – 7 of general formula [{(η 6 - p -iPrC 6 H 4 Me) 2 Ru 2 -(OO\OO)} 2 (bpep) 2 ][OTf] 4 . All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5 – 7 were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6 . Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study.

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Synthesis and antioxidant activity of hydroxylated phenanthrenes as cis-restricted resveratrol analogues

Cited by 34 publications

References 53 publications

Influence of Glucuronidation and Reduction Modifications of Resveratrol on its Biological Activities

Influence of Glucuronidation and Reduction Modifications of Resveratrol on its Biological Activities

Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties

Anticancer activities of self-assembled molecular bowls containing a phenanthrene-based donor and Ru(II) acceptors

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