Pyrano[3,2-a]carbazole alkaloids as effective agents against ischemic stroke in vitro and in vivo

Zang, Yingda; Song, Xiu-Yun; Li, Chuang‐Jun; Ma, Jie; Chu, Shifeng; Liu, Dandan; Ren, Qian; Li, Yan; Chen, Nai‐Hong; Zhang, Dongming

doi:10.1016/j.ejmech.2017.11.084

Cited by 28 publications

(19 citation statements)

References 29 publications

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“…This hypothesis is supported by the following: (1) There is an ample evidence that chronic cerebral hypoperfusion is one of the key factors in the development of cognitive impairment, in which vascular oxidative stress plays a major role [32]. (2) We have confirmed that CZ-7 has a protective effect in H 2 O 2 -induced PC12 cells and primary neuron cells damage in vitro [15]. (3) CZ-7 exhibits strong free radicalscavenging activity [15].…”

Section: Discussionmentioning

confidence: 61%

“…(2) We have confirmed that CZ-7 has a protective effect in H 2 O 2 -induced PC12 cells and primary neuron cells damage in vitro [15]. (3) CZ-7 exhibits strong free radicalscavenging activity [15]. Redox homeostasis in the human body is a complex process, and ROS are involved in the maintenance of redox homeostasis and various cellular signaling pathways.…”

Section: Discussionmentioning

confidence: 63%

“…Preliminary metabolic studies showed that CZ-7 readily passed through the blood-brain barrier and that its exposure in the brain was 4.3 times that of the plasma. In addition, CZ-7 showed strong free radical-scavenging activity [15]. Preliminary acute toxicological test results showed that CZ-7 had no toxic side effects with an oral 1 g/kg dose in ICR mice.…”

Section: Introductionmentioning

confidence: 92%

“…Based on the structure of Clau F, 37 new derivatives (named compounds CZ1-37) were obtained by Dong-Ming Zhang's research group to seek more effective and safer compounds. Preliminary studies on the activity of Clau F and its derivatives showed that the activities of some derivatives were better than that of Clau F. Among them, derivative CZ-7 exhibited the strongest neuroprotective effects in vitro and inhibited programmed death of PC12 cells and primary cortical neurons [15]. Preliminary metabolic studies showed that CZ-7 readily passed through the blood-brain barrier and that its exposure in the brain was 4.3 times that of the plasma.…”

Section: Introductionmentioning

confidence: 99%

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CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses

et al. 2018

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Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. The 2VO rats were orally administered CZ-7 (10, 20, 40 mg/kg) from day 27 to day 53 post-surgery. Morris water maze tests conducted at day 48-51 revealed that CZ-7 administration significantly reduced the escape latency in 2VO rats. After the rats were sacrificed on day 53, morphological studies using Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that administration of CZ-7 markedly attenuated the pathological changes in CA1-CA3 area of the hippocampus, including neuronal cell loss, nuclear shrinkage, and dark staining of neurons, and significantly decreased the chronic cerebral hypoperfusion-induced cell loss. Klüver-Barrera staining study revealed that CZ-7 administration significantly improved the white matter lesions. 8-OHdG and reactive oxygen species (ROS) immunofluorescent analyses showed that CZ-7 administration significantly decreased oxidative stress in CA1-CA3 area of the hippocampus. Finally, we found that the CZ-7-improved oxidative stress might be mediated via the Nrf2 pathway, evidenced by the double immunofluorescent staining of Nrf2 and the elevation of expression levels of oxidative stress proteins HO-1 and NQO1. In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses

et al. 2018

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“…Taken together our findings suggest that compound 13 (3-ethoxy-1-hydroxy-8-methoxy- 2-methylcarbazole-5-carbaldehyde), by having both anti-oxidant ability together and neurogenetic ability, might be beneficial for the treatment of neurological disorders. In fact, various series of carbazole derivatives have been designed and synthesized as neuroprotective therapeutic agents for AD [32], PD [33], ALS [34], ischemic stroke [35] or traumatic brain injury [36] and so on in recent years. We are planning to investigate whether compound 13 has neuroprotective ability in vivo using various disease model mice.…”

Section: Resultsmentioning

confidence: 99%

Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells

et al. 2019

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Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury. Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8- methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury.

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Divergent Total Synthesis of (±)‐Mahanine and Other Carbazole Alkaloids

et al. 2021

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We represent here, a divergent approach for the total synthesis of (�)-Mahanine and twelve other naturally occurring carbazole alkaloids. Remarkably, we have utilized a simplified scalable Suzuki coupling for CÀ C bond formation and a metal-free CÀ N coupling sequence to synthesize the functionalized carbazole scaffold from a single intermediate. Subsequently, either functional group manipulations or late-stage pyran ring annulation furnished a library of 13 carbazole alkaloids mostly isolated from a traditional medicinal plant Murraya koenigii. The construction of carbazole moiety at the initial-stage followed by late-stage pyran annulation under mild condition overcomes the decomposition problem of pyran-ring under acidic or other harsh reaction conditions.

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Pyrano[3,2-a]carbazole alkaloids as effective agents against ischemic stroke in vitro and in vivo

Cited by 28 publications

References 29 publications

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses

CZ-7, a new derivative of Claulansine F, ameliorates 2VO-induced vascular dementia in rats through a Nrf2-mediated antioxidant responses

Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells

Divergent Total Synthesis of (±)‐Mahanine and Other Carbazole Alkaloids

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