Design, synthesis, and evaluation of NDGA analogues as potential anti-ischemic stroke agents

Huang, Lili; Wang, Jiabing; Chen, Liping; Zhu, Min; Wu, Shoubiao; Chu, Shifeng; Zheng, Yuantie; Fan, Zhihai; Zhang, Jiafeng; Li, Wulan; Chen, Dahui; Xiufei, Yang; Wang, Sicen; Qiu, Peihong; Wu, Jianzhang

doi:10.1016/j.ejmech.2017.09.028

Cited by 35 publications

(26 citation statements)

References 38 publications

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“…In general, due to the pretreatment with antioxidants for a short time (within 2 h) followed by H 2 O 2 insult, there is not enough time to induce the expression of cytoprotective protein, and antioxidants may play cytoprotective effect by directly neutralizing ROS 44 . Thus, we chose the screening model of compounds pre-incubation for 1 h to further study the free radical scavenging activity.…”

Section: Resultsmentioning

confidence: 99%

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Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Wang

Huang

Cheng

et al. 2019

Acta Pharmaceutica Sinica B

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Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H 2 O 2 -induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

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Section: Resultsmentioning

confidence: 99%

“…The DPPH assay measured hydrogen atom (or one electron) donating activity and hence provided an evaluation of antioxidant activity due to free radical scavenging 90 . The test was prepared as described previously 44. , 91.…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Wang

Huang

Cheng

et al. 2019

Acta Pharmaceutica Sinica B

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“…This is the case of tetra-O-methyl nordihydroguaiaretic acid, also called Terameprocol, M4N or EM-1421. As shown in Figure 4, in this (Blecha et al, 2007); (D) Re-draw of NDGA-analog reported in (Zhao et al, 2017); (E) Re-draw of NDGA-analog reported in (Huang et al, 2018). molecule the four hydroxyl groups of the two catechol rings have been methylated, thus preventing the formation of catechol quinones.…”

Section: Ndga-analogs As Novel Therapeutic Small Moleculesmentioning

confidence: 81%

“…In ischemic stroke, oxidative damage is a crucial factor. Novel NDGA analogs have been developed that combine potent ROS scavenging and NRF2 activation (Huang et al, 2018). Compound 3a of this study [(2Z, 5E)-2,5-bis (3,4dihydroxybenzylidene)cyclopentanone; Figure 4] was more effective than the antioxidant edaravone in reducing brain infarction after cerebral ischemia-reperfusion injury in rats subjected to transient middle cerebral artery occlusion.…”

Section: Ndga-analogs As Novel Therapeutic Small Moleculesmentioning

confidence: 86%

“…The cyclized NDGA analog has to be capable of oxidation because this fact is critical for preventing a-synuclein aggregation (Daniels et al, 2019). Huang et al (2018) synthesized NDGAanalogs containing curcumin's a, b-unsaturated ketone moiety (Huang et al, 2018). The analogs provided cytoprotection against oxidative damage.…”

Section: Ndga-analogs As Novel Therapeutic Small Moleculesmentioning

confidence: 99%

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Nordihydroguaiaretic Acid: From Herbal Medicine to Clinical Development for Cancer and Chronic Diseases

et al. 2020

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Nordihydroguaiaretic acid (NDGA) is a phenolic lignan obtained from Larrea tridentata, the creosote bush found in Mexico and USA deserts, that has been used in traditional medicine for the treatment of numerous diseases such as cancer, renal, cardiovascular, immunological, and neurological disorders, and even aging. NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals and this may explain part of its therapeutic action. Additional effects include inhibition of lipoxygenases (LOXs) and activation of signaling pathways that impinge on the transcription factor Nuclear Factor Erythroid 2-related Factor (NRF2). On the other hand, the oxidation of the catechols to the corresponding quinones my elicit alterations in proteins and DNA that raise safety concerns. This review describes the current knowledge on NDGA, its targets and side effects, and its synthetic analogs as promising therapeutic agents, highlighting their mechanism of action and clinical projection towards therapy of neurodegenerative, liver, and kidney disease, as well as cancer.

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Analogs of imine resveratrol alleviate oxidative stress‐induced neurotoxicity in PC12 cells via activation of Nrf2

et al. 2021

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Design, synthesis, and evaluation of NDGA analogues as potential anti-ischemic stroke agents

Cited by 35 publications

References 38 publications

Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Nordihydroguaiaretic Acid: From Herbal Medicine to Clinical Development for Cancer and Chronic Diseases

Analogs of imine resveratrol alleviate oxidative stress‐induced neurotoxicity in PC12 cells via activation of Nrf2

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