Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins

This review presents the main properties of hydroxycinnamic acid (HCA) derivatives and their potential application as agents for the prevention and treatment of neurodegenerative diseases. It is partially focused on the successful use of these compounds as inhibitors of amyloidogenic transformation of proteins. Firstly, the prerequisites for the emergence of interest in HCA derivatives, including natural compounds, are described. A separate section is devoted to synthesis and properties of HCA derivatives. Then, the results of molecular modeling of HCA derivatives with prion protein as well as with α-synuclein fibrils are summarized, followed by detailed analysis of the experiments on the effect of natural and synthetic HCA derivatives, as well as structurally similar phenylacetic and benzoic acid derivatives, on the pathological transformation of prion protein and α-synuclein. The ability of HCA derivatives to prevent amyloid transformation of some amyloidogenic proteins, and their presence not only in food products but also as natural metabolites in human blood and tissues, makes them promising for the prevention and treatment of neurodegenerative diseases of amyloid nature.

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403. Studies in light absorption. Part VI. Steric inhibition of resonance in natural and synthetic derivatives of cyclohexene

Journal of the Chemical Society (Resumed) ◽

10.1039/jr9490001890 ◽

1949 ◽

pp. 1890 ◽

Cited By ~ 26

Author(s):

E. A. Braude ◽

E. R. H. Jones ◽

H. P. Koch ◽

R. W. Richardson ◽

F. Sondheimer ◽

...

Keyword(s):

Light Absorption ◽

Steric Inhibition Of Resonance ◽

Synthetic Derivatives ◽

Derivatives Of ◽

Natural And Synthetic

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Identifying binding modes of two synthetic derivatives of adrenalin to the α2C-adrenoceptor by using molecular modeling; insights into the α2C–adrenoceptor activation

Biophysical Chemistry ◽

10.1016/j.bpc.2017.01.005 ◽

2017 ◽

Vol 223 ◽

pp. 17-24 ◽

Cited By ~ 3

Author(s):

Samira Gholami ◽

A. Khalegh Bordbar ◽

Amir Lohrasebi

Keyword(s):

Molecular Modeling ◽

Binding Modes ◽

Synthetic Derivatives ◽

Derivatives Of

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Amyloidogenic metal-binding proteins: new investigative pathways

Biochemical Society Transactions ◽

10.1042/bst0361299 ◽

2008 ◽

Vol 36 (6) ◽

pp. 1299-1303 ◽

Cited By ~ 6

Author(s):

Paul Davies ◽

Sarah N. Fontaine ◽

Dima Moualla ◽

Xiaoyan Wang ◽

Josephine A. Wright ◽

...

Keyword(s):

Amyloid Precursor Protein ◽

Neurodegenerative Diseases ◽

Prion Protein ◽

Metal Binding ◽

Binding Proteins ◽

Normal Function ◽

Amyloidogenic Proteins ◽

Logical Reason ◽

Associated Proteins ◽

Β Amyloid

Neurodegenerative diseases remain perplexing and problematic for modern research. Those associated with amyloidogenic proteins have often been lumped together simply because those proteins aggregate. However, research has identified a more logical reason to group some of these diseases together. The associated proteins not only aggregate, but also bind copper. The APP (amyloid precursor protein) binds copper in an N-terminal region. Binding of copper has been suggested to influence generation of β-amyloid from the protein. PrP (prion protein) binds copper, and this appears to be necessary for its normal function and might also reduce its probability of conversion into an infectious prion. α-Synuclein, a protein associated with Parkinson's disease, also binds copper, but, in this case, it potentially increases the rate at which the protein aggregates. The similarities between these proteins, in terms of metal binding, has allowed us to investigate them using similar approaches. In the present review, we discuss some of these approaches.

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Binding assessment of two arachidonic-based synthetic derivatives of adrenalin with β-lactoglobulin: Molecular modeling and chemometrics approach

Biophysical Chemistry ◽

10.1016/j.bpc.2015.10.001 ◽

2015 ◽

Vol 207 ◽

pp. 97-106 ◽

Cited By ~ 3

Author(s):

S. Gholami ◽

A.K. Bordbar ◽

N. Akvan ◽

H. Parastar ◽

N. Fani ◽

...

Keyword(s):

Molecular Modeling ◽

Synthetic Derivatives ◽

Β Lactoglobulin ◽

Derivatives Of

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Natural and Synthetic Derivatives of Discorhabdin C, a Cytotoxic Pigment from the New Zealand Sponge Latrunculia cf. bocagei

The Journal of Organic Chemistry ◽

10.1021/jo00105a047 ◽

1994 ◽

Vol 59 (26) ◽

pp. 8233-8238 ◽

Cited By ~ 29

Author(s):

Brent R. Copp ◽

Kate F. Fulton ◽

Nigel B. Perry ◽

John W. Blunt ◽

Murray H. G. Munro

Keyword(s):

New Zealand ◽

Synthetic Derivatives ◽

Derivatives Of ◽

Natural And Synthetic

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Kinetics of pyrolysis of natural and synthetic derivatives of cinnamic acid on the surface of nanosilica

Himia Fizika ta Tehnologia Poverhni ◽

10.15407/hftp10.03.281 ◽

2019 ◽

Vol 10 (3) ◽

pp. 281-293

Author(s):

T. V. Kulik ◽

◽

B. B. Palianytsia ◽

N. N. Nastasiienko ◽

S. S. Tarnavskyi ◽

...

Keyword(s):

Cinnamic Acid ◽

Synthetic Derivatives ◽

Kinetics Of ◽

Derivatives Of ◽

Natural And Synthetic

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Synthetic derivatives of pulchrol: An antiparasitic natural product

Planta Medica ◽

10.1055/s-0036-1596772 ◽

2016 ◽

Vol 81 (S 01) ◽

pp. S1-S381

Author(s):

P Terrazas ◽

O Sterner

Keyword(s):

Natural Product ◽

Synthetic Derivatives ◽

Derivatives Of

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Synthesis of New Peptide Derivatives of Galanthamine Designed for Prevention and Treatment of Alzheimer’s Disease

Protein and Peptide Letters ◽

10.2174/0929866522666150701111642 ◽

2015 ◽

Vol 22 (10) ◽

pp. 913-922 ◽

Cited By ~ 2

Author(s):

Lyubomir Vezenkov ◽

Lilia Ilieva ◽

Dancho Danalev ◽

Anastasia Bakalova ◽

D. Vassilev ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Prevention And Treatment ◽

Peptide Derivatives ◽

Derivatives Of

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Synthesis, Cytotoxicity and Antioxidant Activity of New Analogs of RC-121 Synthetic Derivatives of Somatostatin

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180417164344 ◽

2019 ◽

Vol 18 (10) ◽

pp. 1417-1424 ◽

Cited By ~ 2

Author(s):

Emilia Naydenova ◽

Diana Wesselinova ◽

Svetlana Staykova ◽

Ivan Goshev ◽

Ljubomir Vezenkov

Keyword(s):

Antioxidant Activity ◽

Antioxidant Capacity ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Colorectal Cancer Cell Line ◽

Cervical Cancer Cell Line ◽

Synthetic Derivatives ◽

Derivatives Of

Background: Based on the structure of RC-121 (D-Phe-c (Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2, - synthetic derivatives of somatostatin), some analogs were synthesized and tested for in vitro cytotoxic and antioxidant activity. Objectives: The new analogs were modifyed at position 5 with Dap (diaminopropanoic acid), Dab (diaminobutanoic acid) and Orn and at position 6 with the unnatural amino acids Tle (t-leucine). Methods: The in vitro cytotoxic effects of the substances were investigated against a panel of human tumor cell lines HT-29 (Human Colorectal Cancer Cell Line), MDA-MB-23 (Human Breast Cancer Cell Line), Hep G-2 (Human Hepatocellular Carcinoma Cell Line) and HeLa (cervical cancer cell line). The antioxidant capacities were tested by ORAC (Oxygen Radical Antioxidant Capacity) and HORAC (Hydroxyl Radical Averting Capacity) methods. Results: All substances expressed significantly higher antioxidant capacity by comparison with galic acid and Trolox. All substances showed considerable antioxidant capacity as well. Compound 2T (D-Phe-c(Cys-Tyr-DTrp- Dap-Tle-Cys)-Thr-NH2)had the highest antioxidant effect. The compound 4T (D-Phe-c(Cys-Tyr-D-Trp- Orn-Tle-Cys)-Thr-NH2) displayed antiproliferative effect on HeLa cells with IC50 30 µM. The peptide analog 3T (D-Phe-c(Cys-Tyr-D-Trp-Lys-Tle-Cys)-Thr-NH2) exerted the most pronounced inhibition on the cell vitality up to 53%, 56% and 65% resp. against MDA-MB-23, Hep G-2, HeLa in the higher tested concentration. Conclusion: The somatostatin analogs showed moderate influence on the vitality of different tumor cells and could be used in changing their pathology.

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