Synthesis and evaluation of cytotoxic effects of hanultarin and its derivatives

Lee, Eun-Young; Ahamed, V.S. Jamal; Mahto, Sanjeev Kumar; Rhee, Seog Woo; Moon, Surk‐Sik; Hong, In–Sun

doi:10.1016/j.bmcl.2011.09.014

Cited by 7 publications

(11 citation statements)

References 19 publications

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“…The synthesis of the secoisolariciresinol core was performed by a novel, scalable route that has been previously described (16). The purities of synthetic SDG ( S,S ) and SDG ( R,R ) stereoisomers were >95%, as determined by NMR spectroscopy.…”

Section: Methodsmentioning

confidence: 99%

Novel Synthetic (S,S) and (R,R)-Secoisolariciresinol Diglucosides (SDGs) Protect Naked Plasmid and Genomic DNA From Gamma Radiation Damage

Mishra

Pietrofesa

Christofidou‐Solomidou

2014

Radiation Research

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Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain flaxseed. However, extraction methods are complex and are associated with low yield and high costs. Using a novel synthetic pathway, our group succeeded in chemically synthesizing SDG (S,S and R,R enantiomers), which faithfully recapitulates the properties of their natural counterparts, possessing strong antioxidant and free radical scavenging properties. This study further extends initial findings by now investigating the DNA-radioprotective properties of the synthetic SDG enantiomers compared to the commercial SDG. DNA radioprotection was assessed by cell-free systems such as: (a) plasmid relaxation assay to determine the extent of the supercoiled (SC) converted to open-circular (OC) plasmid DNA (pBR322) after exposure of the plasmid to gamma radiation; and (b) determining the extent of genomic DNA fragmentation. Exposure of plasmid DNA to 25 Gy of γ radiation resulted in decreased supercoiled form and increased open-circular form, indicating radiation-induced DNA damage. Synthetic SDG (S,S) and SDG (R,R), and commercial SDG at concentrations of 25–250 μM significantly and equipotently reduced the radiation-induced supercoiled to open-circular plasmid DNA in a dose-dependent conversion. In addition, exposure of calf thymus DNA to 50 Gy of gamma radiation resulted in DNA fragments of low-molecular weight (<6,000 bps), which was prevented in a dose-dependence manner by all synthetic and natural SDG enantomers, at concentrations as low as 0.5 μM. These novel results demonstrated that synthetic SDG (S,S) and SDG (R,R) isomers and commercial SDG possess DNA-radioprotective properties. Such properties along with their antioxidant and free radical scavenging activity, reported earlier, suggest that SDGs are promising candidates for radioprotection for normal tissue damage as a result of accidental exposure during radiation therapy for cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Novel Synthetic (S,S) and (R,R)-Secoisolariciresinol Diglucosides (SDGs) Protect Naked Plasmid and Genomic DNA From Gamma Radiation Damage

Mishra

Pietrofesa

Christofidou‐Solomidou

2014

Radiation Research

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“…Compounds 104 and 105 inhibited NO release by LPS-activated microglia cells. 44 Schisandrosides A-D (108)(109)(110)(111) were also isolated from S. chinensis. Although they demonstrated no cytotoxicity against endometrial cancer cells using 3-4,5dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assays, they represent the rst examples of natural dibenzocyclooctadiene lignan glucosides.…”

Section: Dibenzocyclooctadiene Derivativesmentioning

confidence: 99%

Recent advances in research on lignans and neolignans

2016

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Covering: 2009 to 2015Lignans and neolignans are a large group of natural products derived from the oxidative coupling of two C6-C3 units. Owing to their biological activities ranging from antioxidant, antitumor, anti-inflammatory to antiviral properties, they have been used for a long time both in ethnic as well as in conventional medicine. This review describes 564 of the latest examples of naturally occurring lignans and neolignans, and their glycosides in some cases, which have been isolated between 2009 and 2015. It comprises the data reported in more than 200 peer-reviewed articles and covers their source, isolation, structure elucidation and bioactivities (where available), and highlights the biosynthesis and total synthesis of some important ones.

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“…A double Stobbe condensation 19 has been used to prepare racemic secoisolariciresinol and enantioenriched secoisolariciresinols have been prepared from aldol reactions on chiral γ-butyrolactones 20 as well as diasteroselective alkylation of Evans auxiliary appended hydroferulic acid derivatives. 21 In a recent report the synthesis of ( S , S )-SDG- 1 was claimed.…”

mentioning

confidence: 99%

“…Thus, following a modified literature procedure, 19 3 was subjected to Stobbe condensation with dimethyl succinate in the presence of lithium wire in refluxing methanol, and the resulting mixture of carboxylic acids was esterified with methanol under acidic conditions to furnish dimethyl ester 4 in 70% overall yield (single isomer, unassigned olefin geometry). A second Stobbe condensation involving product 4 with vanillin under the same lithium-mediated conditions, followed by esterification with methanol under the same acidic conditions, led to diene 5 in 61% overall yield (single isomer, unassigned olefin geometry).…”

mentioning

confidence: 99%

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

Mishra

Simmons

Tyagi

et al. 2013

Bioorganic & Medicinal Chemistry Letters

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Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC50 = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively) which compared well with that of natural (S,S)-SDG-1 (EC50 = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC50 = 1129.32 ± 88.79 μM) and α-tocopherol (EC50 = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC50 = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC50 = 157.54 ± 21.30; synthetic (R,R)-SDG-2: EC50 = 123.63 ± 8.67] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use.

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Synthesis and evaluation of cytotoxic effects of hanultarin and its derivatives

Cited by 7 publications

References 19 publications

Novel Synthetic (S,S) and (R,R)-Secoisolariciresinol Diglucosides (SDGs) Protect Naked Plasmid and Genomic DNA From Gamma Radiation Damage

Novel Synthetic (S,S) and (R,R)-Secoisolariciresinol Diglucosides (SDGs) Protect Naked Plasmid and Genomic DNA From Gamma Radiation Damage

Recent advances in research on lignans and neolignans

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

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