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  1. Article ; Online: Immunosuppressive properties of amino acid and peptide derivatives of mycophenolic acid.

    Siebert, Agnieszka / Cholewiński, Grzegorz / Trzonkowski, Piotr / Rachon, Janusz

    European journal of medicinal chemistry

    2020  Volume 189, Page(s) 112091

    Abstract: Mycophenolic acid (MPA) was coupled with amino acids and biologically active peptides including derivatives of tuftsin to modify its immunosuppressive properties. Both amino acid unit in the case of simple MPA amides and modifications within peptide ... ...

    Abstract Mycophenolic acid (MPA) was coupled with amino acids and biologically active peptides including derivatives of tuftsin to modify its immunosuppressive properties. Both amino acid unit in the case of simple MPA amides and modifications within peptide moiety of MPA - tuftsin conjugates influenced the observed activity. Antiproliferative potential of the obtained conjugates was investigated in vitro and MPA amides with threonine methyl ester and conjugate of MPA with retro-tuftisin occurred to be more selective against PBMC in comparison to parent MPA. Both amino acid and peptide derivatives of MPA acted as inosine-5'-monophosphate dehydrogenaze (IMPDH) inhibitors.
    MeSH term(s) Amino Acids/chemistry ; Cell Proliferation ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; IMP Dehydrogenase/antagonists & inhibitors ; Immunosuppressive Agents/chemistry ; Immunosuppressive Agents/pharmacology ; Jurkat Cells ; Leukocytes, Mononuclear/drug effects ; Molecular Structure ; Mycophenolic Acid/chemistry ; Peptide Fragments/chemistry ; Structure-Activity Relationship
    Chemical Substances Amino Acids ; Enzyme Inhibitors ; Immunosuppressive Agents ; Peptide Fragments ; IMP Dehydrogenase (EC 1.1.1.205) ; Mycophenolic Acid (HU9DX48N0T)
    Language English
    Publishing date 2020-01-24
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2020.112091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 784: Show issues Location:
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  2. Article ; Online: Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid.

    Siebert, Agnieszka / Deptuła, Milena / Cichorek, Mirosława / Ronowska, Anna / Cholewiński, Grzegorz / Rachon, Janusz

    Anti-cancer agents in medicinal chemistry

    2020  Volume 21, Issue 4, Page(s) 462–467

    Abstract: Background: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant, it also possesses anticancer activity. MPA acts as Inosine-5'-Monophosphate Dehydrogenase (IMPDH) inhibitor, where the carboxylic group at the end of ... ...

    Abstract Background: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant, it also possesses anticancer activity. MPA acts as Inosine-5'-Monophosphate Dehydrogenase (IMPDH) inhibitor, where the carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too. On the other hand, potent anticancer agents like dacarbazine and cisplatin give numerous side-effects.
    Objective: Based on the literature data, MPA derivatives should be explored towards anticancer properties. Conversion of the carboxylic group of MPA to amide could maintain antiproliferative activity. Therefore, we decided to investigate several amino acid and peptide derivatives of MPA against chosen cancer cell lines in vitro.
    Methods: Amides of MPA hold threonine and arginine amino acid unit. These amino acid derivatives were tested as L and D enantiomers and both in free acid and methyl esters forms. Additionally, MPA was modified with tuftsin or retro-tuftsin as biologically active peptides, which could act as a drug carrier.
    Results: Amino acid and peptide derivatives of MPA were investigated in vitro as potential anticancer agents on cell lines: Ab melanoma, A375 melanoma and SHSY5Y neuroblastoma. The activity of the tested compounds was compared to parent MPA and known chemotherapeutics: dacarbazine and cisplatin.
    Conclusion: Amino acid moiety and the sequence of amino acids in the peptide part influenced observed activity. The most active amino acid MPA analogues occurred to be D and L-threonine derivatives as methyl esters, probably due to better cell membrane penetration.
    MeSH term(s) Amino Acids/chemical synthesis ; Amino Acids/chemistry ; Amino Acids/pharmacology ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Humans ; Mitochondria/drug effects ; Molecular Structure ; Mycophenolic Acid/chemical synthesis ; Mycophenolic Acid/chemistry ; Mycophenolic Acid/pharmacology ; Peptides/chemical synthesis ; Peptides/chemistry ; Peptides/pharmacology ; Structure-Activity Relationship
    Chemical Substances Amino Acids ; Antineoplastic Agents ; Peptides ; Mycophenolic Acid (HU9DX48N0T)
    Language English
    Publishing date 2020-05-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2217610-X
    ISSN 1875-5992 ; 1871-5206
    ISSN (online) 1875-5992
    ISSN 1871-5206
    DOI 10.2174/1871520620666200516151456
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5583: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: New Analogues of Mycophenolic Acid.

    Siebert, Agnieszka / Prejs, Michal / Cholewinski, Grzegorz / Dzierzbicka, Krystyna

    Mini reviews in medicinal chemistry

    2017  Volume 17, Issue 9, Page(s) 734–745

    Abstract: Background: Mycophenolic acid (MPA) possesses antibacterial, antifungal, antiviral, immunosuppressive and anticancer properties. It is a non-competitive and reversible inhibitor of dehydrogenase inosine-5'-monophosphate (IMPDH). This compound belongs to ...

    Abstract Background: Mycophenolic acid (MPA) possesses antibacterial, antifungal, antiviral, immunosuppressive and anticancer properties. It is a non-competitive and reversible inhibitor of dehydrogenase inosine-5'-monophosphate (IMPDH). This compound belongs to the immunosuppressive drugs used for the prevention of both acute and chronic transplant rejection. Until now, two derivatives of MPA have been used clinically: mycophenolate mofetil (MMF, CellCept) and mycophenolate sodium (MPS, Myfortic). They cause, similar to MPA, although at lower degree, the side effects such as vomiting, abdominal pain, diarrhea, nausea, gastrointestinal, urogenital tract, blood or nervous system disorders. These drawbacks and glucuronidation of MPA in vivo limit the use of these compounds as pharmaceuticals. Therefore, research is still going on for more effective analogs that are less toxic to the organism and could improve the quality of life of patients.
    Conclusion: In this review article, the authors present the synthesis of novel derivatives of mycophenolic acid, together with their initial biological investigations.
    MeSH term(s) Graft Rejection/drug therapy ; Humans ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/chemistry ; Immunosuppressive Agents/therapeutic use ; Molecular Structure ; Mycophenolic Acid/adverse effects ; Mycophenolic Acid/chemistry ; Mycophenolic Acid/therapeutic use
    Chemical Substances Immunosuppressive Agents ; Mycophenolic Acid (HU9DX48N0T)
    Language English
    Publishing date 2017
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2104081-3
    ISSN 1875-5607 ; 1389-5575
    ISSN (online) 1875-5607
    ISSN 1389-5575
    DOI 10.2174/1389557516666161129160001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5891: Show issues Location:
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  4. Article ; Online: Tuftsin - Properties and Analogs.

    Siebert, Agnieszka / Gensicka-Kowalewska, Monika / Cholewiński, Grzegorz / Dzierzbicka, Krystyna

    Current medicinal chemistry

    2017  

    Abstract: Immunomodulation is one of the significant therapeutic strategies. It includes both stimulation or suppression of the immune system by a variety of substances called immunomodulators, designed to regulate the immune response of the organism to infections ...

    Abstract Immunomodulation is one of the significant therapeutic strategies. It includes both stimulation or suppression of the immune system by a variety of substances called immunomodulators, designed to regulate the immune response of the organism to infections of varying etiology. An example of such a substance is tuftsin (TKPA) 3 (Fig. (1)). Tuftsin is an endogenous immunomodulator of a wide spectrum of biological activity. Tetrapeptide 3 provides also antitumor, antimicrobial, anticoagulant and analgesic properties. In this paper, we presented tuftsin derivatives described over the years, its biological activity and potential clinical applications.
    Language English
    Publishing date 2017-07-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1319315-6
    ISSN 1875-533X ; 0929-8673
    ISSN (online) 1875-533X
    ISSN 0929-8673
    DOI 10.2174/0929867324666170725140826
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4432: Show issues Location:
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  5. Article ; Online: Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid.

    Siebert, Agnieszka / Wysocka, Magdalena / Krawczyk, Beata / Cholewiński, Grzegorz / Rachoń, Janusz

    European journal of medicinal chemistry

    2017  Volume 143, Page(s) 646–655

    Abstract: The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid ... ...

    Abstract The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide derivatives proved to be the most versatile ones, their MIC values relative to most strains was lower than MPA alone. It has been noted that the activity of amino acid derivatives depends on the configuration at the chiral center in the amino acid unit and methyl esters indicated better antimicrobial activity than analogs with free carboxylic group.
    MeSH term(s) Amino Acids/chemistry ; Amino Acids/pharmacology ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Dose-Response Relationship, Drug ; Escherichia coli/drug effects ; Klebsiella pneumoniae/drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Mycophenolic Acid/chemical synthesis ; Mycophenolic Acid/chemistry ; Mycophenolic Acid/pharmacology ; Peptides/chemistry ; Peptides/pharmacology ; Pseudomonas aeruginosa/drug effects ; Staphylococcus aureus/drug effects ; Structure-Activity Relationship
    Chemical Substances Amino Acids ; Anti-Bacterial Agents ; Peptides ; Mycophenolic Acid (HU9DX48N0T)
    Keywords covid19
    Language English
    Publishing date 2017-12-01
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2017.11.094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 784: Show issues Location:
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  6. Article ; Online: New conjugates of mycophenolic acid and their antiproliferative activity.

    Prejs, Michał / Cholewinski, Grzegorz / Siebert, Agnieszka / Trzonkowski, Piotr / Dzierzbicka, Krystyna

    Journal of Asian natural products research

    2016  Volume 18, Issue 11, Page(s) 1057–1062

    Abstract: The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of N(6)-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds 4a-h were evaluated on leukemia cell line (Jurkat) and PBMC from healthy ... ...

    Abstract The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of N(6)-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds 4a-h were evaluated on leukemia cell line (Jurkat) and PBMC from healthy donors. Length of the linker influenced observed activity. The compound 4b possessing 1,3-diamine spacer exhibited the most promising results and can be considered to further investigations.
    MeSH term(s) Adenosine/analogs & derivatives ; Adenosine/chemical synthesis ; Adenosine/chemistry ; Adenosine/pharmacology ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Leukocytes, Mononuclear ; Molecular Structure ; Mycophenolic Acid/chemistry
    Chemical Substances Antineoplastic Agents ; Mycophenolic Acid (HU9DX48N0T) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2016-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2077926-4
    ISSN 1477-2213 ; 1028-6020
    ISSN (online) 1477-2213
    ISSN 1028-6020
    DOI 10.1080/10286020.2016.1184653
    Database MEDical Literature Analysis and Retrieval System OnLINE

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