Facile synthesis of deuterated and [<sup>14</sup>C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools

Gordon, Odaine N.; Graham, Leigh Ann; Schneider, Claus

doi:10.1002/jlcr.3102

Cited by 20 publications

(25 citation statements)

References 22 publications

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“…Thus, DMC and BDMC were prepared by chemical synthesis 17, 18 and their rates of degradation were determined. The degradation of the pure compounds was too slow for continuous recording using the UV/Vis spectrophotometric assay.…”

Section: Resultsmentioning

confidence: 99%

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα

Gordon

Luis

Ashley

et al. 2015

Chem. Res. Toxicol.

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102

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Extracts from the rhizome of the turmeric plant are widely consumed as anti-inflammatory dietary supplements. Turmeric extract contains the three curcuminoids, curcumin (≈80% relative abundance), demethoxycurcumin (DMC; ≈15%), and bisdemethoxycurcumin (BDMC; ≈5%). A distinct feature of pure curcumin is its instability at physiological pH resulting in rapid autoxidation to a bicyclopentadione within 10–15 min. Here, we describe oxidative transformation of turmeric extract, DMC, and BDMC, and the identification of their oxidation products using LC-MS and NMR analyses. DMC autoxidized over the course of 24 h to the expected bicyclopentadione diastereomers. BDMC was resistant to autoxidation, and oxidative transformation required catalysis by horseradish peroxidase and H2O2 or potassium ferricyanide. The product of BDMC oxidation was a stable spiroepoxide that was equivalent to a reaction intermediate in the autoxidation of curcumin. The ability of DMC and BDMC to poison recombinant human topoisomerase IIα was significantly increased in the presence of potassium ferricyanide indicating that oxidative transformation was required to achieve full DNA cleavage activity. DMC and BDMC are less prone to autoxidation than curcumin and contribute to the enhanced stability of turmeric extract at physiological pH. Their oxidative metabolites may contribute to the biological effects of turmeric extract.

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Section: Resultsmentioning

confidence: 99%

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα

Gordon

Luis

Ashley

et al. 2015

Chem. Res. Toxicol.

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102

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“…13 C-kaempferol was obtained from IsoLife and D 6 -curcumin and D 3 -ferulic acid were purchased from SynInnova. 13 C 12 -curcumin was synthesized from 13 C 6 -vanillin (Cambridge Isotopes Laboratories Inc) following a published procedure [16]. Standards of Q 4 , Q 6 , Q 9 and Q 10 were purchased from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor

Fernández-del-Rio

Nag²,

Casado

et al. 2017

Free Radical Biology and Medicine

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Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q10, but due to its highly lipophilic nature, Q10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4′ of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney.

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“…5 S ‐HETE was synthesized as described, with minor modifications (19, 24). Curcumin was synthesized as described (25). Recombinant human COX‐2 was expressed in Sf9 insect cells (26).…”

Section: Methodsmentioning

confidence: 99%

Roles of 5‐lipoxygenase and cyclooxygenase‐2 in the biosynthesis of hemiketals E₂and D₂by activated human leukocytes

Giménez‐Bastida

Shibata

Uchida³

et al. 2017

FASEB j.

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The 2 hemiketal (HK) eicosanoids HKD and HKE are the major products of the biosynthetic crossover of the 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) pathways. HKs result from the rearrangement of a di-endoperoxide intermediate formed in the COX-2-dependent oxygenation of 5-hydroxyeicosatetraenoic acid (5-HETE). We analyzed HK biosynthesis in human leukocytes stimulated and defined the biosynthetic roles of 5-LOX and COX-2, using inhibitors and incubations with exogenous substrates. Activation of leukocytes with LPS followed by treatment with the calcium ionophore A23187 resulted in the formation of PGE, 5-HETE, and LTB as the principal metabolites of COX-2 and 5-LOX, respectively. The formation of HKD and HKE was highest after 15 min LPS treatment, and at that time, levels were similar to PGE, but less than 5-HETE and LTB The time course of HK formation paralleled that of 5-HETE and LTB, implying the availability of the 5-HETE substrate as a limiting factor in biosynthesis rather than expression levels of COX-2. Specific inhibitors of COX-2 and 5-LOX decreased formation of HKD and HKE Platelets did not form HKs from exogenous 5-HETE, implying that COX-1 is not involved. HKs are early products during an inflammatory event and require cells that express 5-LOX and COX-2 for their biosynthesis.-Giménez-Bastida, J. A., Shibata, T., Uchida, K., Schneider, C. Roles of 5-lipoxygenase and cyclooxygenase-2 in the biosynthesis of hemiketals E and D by activated human leukocytes.

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Facile synthesis of deuterated and [¹⁴C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools

Cited by 20 publications

References 22 publications

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor

Roles of 5‐lipoxygenase and cyclooxygenase‐2 in the biosynthesis of hemiketals E₂and D₂by activated human leukocytes

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Facile synthesis of deuterated and [14C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools

Cited by 20 publications

References 22 publications

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα

Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor

Roles of 5‐lipoxygenase and cyclooxygenase‐2 in the biosynthesis of hemiketals E2and D2by activated human leukocytes

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Facile synthesis of deuterated and [¹⁴C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools

Roles of 5‐lipoxygenase and cyclooxygenase‐2 in the biosynthesis of hemiketals E₂and D₂by activated human leukocytes