Ferulic acid–carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents

Fang, Lei; Chen, Mohao; Liu, Zhikun; Fang, Xubin; Gou, Shaohua; Chen, Li

doi:10.1016/j.bmc.2016.01.010

Cited by 38 publications

(13 citation statements)

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“…Ferulic acid was reported to hybridise with quinoline in a competitive manner. Carbazole was reported to be more potent than galantamine, which showed pronounced inhibition against cholinesterases [46,47]. On the other hand, it was also reported that corilagin (IC 50 = 1.231 mM) was active against tyrosinase [48].…”

Section: Resultsmentioning

confidence: 99%

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

et al. 2020

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Bridelia species have been used in traditional African medicine for the management of diverse human ailments. In the current work, the detailed phytochemical profiles of the extracts of the stem bark of B. speciosa were evaluated and the antioxidant and enzyme inhibitory properties of the extracts were assessed. The anti-bacterial and anti-mycotic effects of the extracts were evaluated against selected pathogen strains. Additionally, the anti-proliferative effects were studied on the liver cancer HepG2 cell line. Finally, the putative protective effects were assessed on isolated rat liver that was challenged with lipopolysaccharide (LPS). The results revealed the presence of 36 compounds in the ethyl acetate extract, 44 in the methanol extract, and 38 in the water extract. Overall, the methanol extract showed the highest antioxidant activity, particularly in LPS-stimulated rat liver. Additionally, this extract exerted the highest antimycotic effect on C. albicans, whereas the water extract showed a promising anti-proliferative effect on liver cancer HepG2 cells. The methanol extract was also the most active as enzyme inhibitor, against acetylcholinesterase and butyrylcholinesterase. The current study appraises the antioxidant and enzyme inhibition properties of B. speciosa methanol extract and showed that this specie could be a promising source of biologically active phytochemicals, with potential health uses. Supplementary Materials: The following are available online at http://www.mdpi.com/2076-3921/9/2/128/s1. Supplementary Materials and Methods; CFF-strains. Author Contributions: Conceptualization, C.F. and G.Z.; methodology, G.O.; L.M.; software, L.M.; validation,: C.F.; G.Z.; L.M.; G.O.; formal analysis, C.F.; G.Z.; investigation, K.I.S.; K.B.; S.L.; L.R.; A.C. (Annalisa Chiavaroli); S.V.; P.A.; V.H.; S.C.; R.V.; L.D.L.; A.C. (Alessandro Cama); M.C.N.P.-A.; Z.C.; J.J.; M.F.M.; resources, C.F.; G.O.; L.M.; data curation, C.F.; G.Z.; writing-original draft preparation, M.F.M.; writing-review and editing, C.F., G.Z.; G.O.; L.M.; visualization, L.B.; supervision, L.B.; project administration, C.F.; L.M.; G.O.; G.Z.; funding acquisition, C.F.; G.O.; L.M. All authors have read and agreed to the published version of the manuscript.

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Section: Resultsmentioning

confidence: 99%

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

et al. 2020

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“…FA has been identified in Chinese medicine herbs such as Angelica sinensis , Cimicifuga heracleifolia and Ligusticum chuangxiong [ 9 , 10 ]. In the previous studies, FA is an effective antioxidant agent that protects DNA from oxidative damage and prevents lipid peroxidation through reducing oxidative stress [ 11 ]. In many tumor cell lines such as human osteosarcoma, human glioblastoma (U87MG), and prostate cancer, FA can induce cytotoxicity [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells

et al. 2018

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BackgroundFerulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a hydroxycinnamic acid derived from a rich polyphenolic compound. This study aimed to investigate the effect of ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA) on cell proliferation, invasion, apoptosis, and autophagy in Hela and Caski cervical carcinoma cell lines.MethodsThe cell proliferation of FA in Hela and Caski cells were detected by MTT assay. The cell invasion of FA in Hela and Caski cells were detected by Transwell assay. Subsequently, MMP-9 mRNA expression for cell invasion was detected by RT-PCR. Additionally, cell cycle and apoptosis were assayed using flow cytometry. Expression levels of 7 proteins for both cell cycle and autophagy were measured by Western blot analysis.ResultsAfter treated with FA (2.0 mM) for 48 h, the inhibition rates of FA in Hela and Caski cells were 88.3 and 85.4%, respectively. In addition, FA inhibited cell invasion through reducing MMP-9 mRNA expression. FA induced arrest in G0/G1 phase of the cell cycle in Hela and Caski cells with dose dependent (P < 0.05). Meanwhile, FA induced the cell cycle-related proteins expression such as p53 and p21, and reduced Cyclin D1 and Cyclin E levels. Moreover, FA decreased the autophagy-related proteins such as LC3-II, Beclin1 and Atg12-Atg5 in a dose-dependent manner.ConclusionFA can significantly inhibit cell proliferation and invasion in Hela and Caski cells. It might be acted as an anti-cancer drug through inhibiting the autophagy and inducing cell cycle arrest in human cervical carcinoma cells.

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“…9 H -Carbazole ( 110 ) and its derivatives are well-known inhibitors of Aβ-aggregation. Some 9 H -carbazole derivatives with substituents in the positions 2 and 8 have been described for their capability for inhibiting AChE and neuroprotection [ 133 ].…”

Section: Molecular Hybrids Designed As Prototypes Of Drug Candidates mentioning

confidence: 99%

“…As a result, a new series of amide hybrids of ferulic acid and 9 H -carbazole was designed, and compound 111a (Fig. 45 ) identified as the best AChEI (IC 50 = 1.9 µM), with higher potency than galantamine, with significant antioxidant and neuroprotective properties [ 133 ].…”

Section: Molecular Hybrids Designed As Prototypes Of Drug Candidates mentioning

confidence: 99%

Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases

Gontijo

Viegas

Ortiz

et al. 2020

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Neurodegenerative Diseases (NDs) are progressive multifactorial neurological pathologies related to neuronal impairment and functional loss from different brain regions. Currently, no effective treatments are available for any NDs, and this lack of efficacy has been attributed to the multitude of interconnected factors involved in their pathophysiology. In the last two decades, a new approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDLs) strategy, has emerged and has been used in the design and for the development of a variety of hybrid compounds capable to act simultaneously in diverse biological targets. Based on the polypharmacology concept, this new paradigm has been thought as a more secure and effective way for modulating concomitantly two or more biochemical pathways responsible for the onset and progress of NDs, trying to overcome low therapeutical effectiveness. As a complement to our previous review article (Curr. Med. Chem. 2007, 14 (17), 1829-1852. https://doi.org/10.2174/092986707781058805), herein we aimed to cover the period from 2008 to 2019 and highlight the most recent advances of the exploitation of Molecular Hybridization (MH) as a tool in the rational design of innovative multifunctional drug candidate prototypes for the treatment of NDs, specially focused on AD, PD, HD and ALS.

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Ferulic acid–carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents

Cited by 38 publications

References 11 publications

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

Bridelia speciosa Müll.Arg. Stem bark Extracts as a Potential Biomedicine: From Tropical Western Africa to the Pharmacy Shelf

The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells

Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases

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