Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains
An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained pepti...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/11/3633 |
| _version_ | 1827664576510951424 |
|---|---|
| author | Parul Sahrawat Paweł Kowalczyk Dominik Koszelewski Mateusz Szymczak Karol Kramkowski Aleksandra Wypych Ryszard Ostaszewski |
| author_facet | Parul Sahrawat Paweł Kowalczyk Dominik Koszelewski Mateusz Szymczak Karol Kramkowski Aleksandra Wypych Ryszard Ostaszewski |
| author_sort | Parul Sahrawat |
| collection | DOAJ |
| description | An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model <i>E. coli</i> bacteria strains (k12, R2–R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics. |
| first_indexed | 2024-03-10T01:02:54Z |
| format | Article |
| id | doaj.art-cddf2b0061cc447bb1c3ab1d75ddbe99 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:02:54Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-cddf2b0061cc447bb1c3ab1d75ddbe992023-11-23T14:31:58ZengMDPI AGMolecules1420-30492022-06-012711363310.3390/molecules27113633Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> StrainsParul Sahrawat0Paweł Kowalczyk1Dominik Koszelewski2Mateusz Szymczak3Karol Kramkowski4Aleksandra Wypych5Ryszard Ostaszewski6Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, PolandDepartment of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, PolandInstitute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, PolandDepartment of Molecular Virology, Faculty of Biology, Institute of Microbiology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, PolandDepartment of Physical Chemistry, Medical University of Bialystok, Kilińskiego 1 Str., 15-089 Białystok, PolandCentre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University in Torun, ul. Wileńska 4, 87-100 Toruń, PolandInstitute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, PolandAn efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model <i>E. coli</i> bacteria strains (k12, R2–R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.https://www.mdpi.com/1420-3049/27/11/3633cyclic peptideugi multicomponent reactiondiketopiperazinesantimicrobial activityminimal inhibitory concentration |
| spellingShingle | Parul Sahrawat Paweł Kowalczyk Dominik Koszelewski Mateusz Szymczak Karol Kramkowski Aleksandra Wypych Ryszard Ostaszewski Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains Molecules cyclic peptide ugi multicomponent reaction diketopiperazines antimicrobial activity minimal inhibitory concentration |
| title | Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains |
| title_full | Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains |
| title_fullStr | Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains |
| title_full_unstemmed | Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains |
| title_short | Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in <i>E</i>. <i>coli</i> Strains |
| title_sort | influence of open chain and cyclic structure of peptidomimetics on antibacterial activity in i e i i coli i strains |
| topic | cyclic peptide ugi multicomponent reaction diketopiperazines antimicrobial activity minimal inhibitory concentration |
| url | https://www.mdpi.com/1420-3049/27/11/3633 |
| work_keys_str_mv | AT parulsahrawat influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains AT pawełkowalczyk influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains AT dominikkoszelewski influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains AT mateuszszymczak influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains AT karolkramkowski influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains AT aleksandrawypych influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains AT ryszardostaszewski influenceofopenchainandcyclicstructureofpeptidomimeticsonantibacterialactivityinieiicoliistrains |