Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation

Du, Hongtao; Jiang, Xiaolong; Ma, Meng; Xu, Hui; Liu, Shuang; Ma, Fang

doi:10.1016/j.bmcl.2020.127659

Cited by 13 publications

(2 citation statements)

References 29 publications

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“…The plant’s active alkaloidal constituents include vasicine, l-vasicinone, deoxyvasicine, maiontone, vasicinolone, and vasicinol, among others, which have been extensively explored for a variety of pharmacological uses. Previously these molecules were explored for various antibacterial [ 22 ] and anti-neurodegenerative disorders [ 23 ] in in silico models. Therefore, these phytoconstituents were chosen for the molecular docking investigation [ 24 , 25 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

In Vitro Anticancer Activity of Methanolic Extract of Justicia adhatoda Leaves with Special Emphasis on Human Breast Cancer Cell Line

et al. 2022

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Natural products are being targeted as alternative anticancer agents due to their non-toxic and safe nature. The present study was conducted to explore the in vitro anticancer potential of Justicia adhatoda (J. adhatoda) leaf extract. The methanolic leaf extract was prepared, and the phytochemicals and antioxidant potential were determined by LCMS analysis and DPPH radical scavenging assay, respectively. A docking study performed with five major alkaloidal phytoconstituents showed that they had a good binding affinity towards the active site of NF-κB. Cell viability assay was carried out in five different cell lines, and the extract exhibited the highest cytotoxicity in MCF-7, a breast cancer cell line. Extract-treated cells showed a significant increase in nitric oxide and reactive oxygen species production. Cell cycle analysis showed an arrest in cell growth at the Sub-G0 phase. The extract successfully inhibited cell migration and colony formation and altered mitochondrial membrane potential. The activities of superoxide dismutase and glutathione were also found to decrease in a dose-dependent manner. The percentage of apoptotic cells was found to increase in a dose-dependent manner in MCF-7 cells. The expressions of caspase-3, Bax, and cleaved-PARP were increased in extract-treated cells. An increase in the expression of NF-κB was found in the cytoplasm in extract-treated cells. J. adhatoda leaf extract showed a potential anticancer effect in MCF-7 cells.

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Section: Resultsmentioning

confidence: 99%

In Vitro Anticancer Activity of Methanolic Extract of Justicia adhatoda Leaves with Special Emphasis on Human Breast Cancer Cell Line

et al. 2022

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“…Some β-carboline alkaloids act as AChE and Aβ inhibitors for the treatment of Alzheimer's disease, but the detailed action mechanism is not well interpreted. [36][37][38] Therefore, it will be very meaningful if the two important plant extracts, harmine and harmol, can be applied to prevent the amyloidosis related to T2DM.…”

Section: Introductionmentioning

confidence: 99%

β‐Carboline Alkaloids Resist the Aggregation and Cytotoxicity of Human Islet Amyloid Polypeptide

et al. 2023

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β‐carboline alkaloids have a variety of pharmacological activities, such as anti‐tumor, antibiosis and anti‐diabetes. Harmine and harmol are two structurally similar β‐carbolines that occur in many medicinal plants. In this work, we chose harmine and harmol to impede the amyloid fibril formation of human islet amyloid polypeptide (hIAPP) associated with type 2 diabetes mellitus (T2DM), by a series of physicochemical and biochemical methods. The results indicate that harmine and harmol effectively prevent peptide fibrillation and alleviate toxic oligomer species. In addition, both small molecules exhibit strong binding affinities with hIAPP mainly through hydrophobic and hydrogen bonding interactions, reducing the cytotoxicity induced by hIAPP. Their distinct binding pattern with hIAPP is closely linked to the molecular configuration of two small molecules, affecting their ability to impede peptide aggregation. The study is of great significance for the application and development of β‐carboline alkaloids against T2DM.

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Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure–activity relationship

Gaur,

Singh,

Sharma

et al. 2024

Archiv der Pharmazie

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Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment. Presently marketed medications include memantine, an N‐methyl‐d‐aspartate receptor (NMDA) antagonist, and acetylcholinesterase (AChE) inhibitors: rivastigmine, donepezil, and galantamine. Unfortunately, these medications are only useful in the initial stages of AD. The mentioned medications only provide symptomatic relief and do not slow down the disease progression in the advanced stages. Therefore, there is an urgent need to develop potential candidates to treat AD, symptomatically and therapeutically. Many research groups focus on natural products due to their diverse therapeutic profiles and easy availability. One such natural product is deoxyvasicinone, isolated from Adhatoda vasica. Given its broad pharmacological profile, various researchers have developed semisynthetic hybrids of deoxyvasicinone to address multifaceted diseases like AD. In this review article, we tried to summarize the semisynthetic hybrids of deoxyvasicinone developed over the past decade (2014–2024) for managing AD. We focus on their design, pharmacological activity, and structure–activity relationship (SAR) analysis. We hope this review enhances the reader's understanding of future exploratory options for deoxyvasicinone hybrids in AD management.

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Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation

Cited by 13 publications

References 29 publications

In Vitro Anticancer Activity of Methanolic Extract of Justicia adhatoda Leaves with Special Emphasis on Human Breast Cancer Cell Line

In Vitro Anticancer Activity of Methanolic Extract of Justicia adhatoda Leaves with Special Emphasis on Human Breast Cancer Cell Line

β‐Carboline Alkaloids Resist the Aggregation and Cytotoxicity of Human Islet Amyloid Polypeptide

Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure–activity relationship

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