Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives
Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel <i>N<...
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/12/2934 |
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doaj-4c90f2e82adf40249be2c163a8f3f0d32020-11-25T02:59:25ZengMDPI AGMolecules1420-30492020-06-01252934293410.3390/molecules25122934Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones DerivativesEdward Krzyżak0Dominika Szkatuła1Benita Wiatrak2Tomasz Gębarowski3Aleksandra Marciniak4Department of Inorganic Chemistry, Wroclaw Medical University, ul. Borowska 211a, 50–556 Wrocław, PolandDepartment of Medicinal Chemistry, Wroclaw Medical University, Borowska 211, 50–556 Wroclaw, PolandDepartment of Basic Medical Sciences, Wroclaw Medical University, Borowska 211, 50–556 Wroclaw, PolandDepartment of Basic Medical Sciences, Wroclaw Medical University, Borowska 211, 50–556 Wroclaw, PolandDepartment of Inorganic Chemistry, Wroclaw Medical University, ul. Borowska 211a, 50–556 Wrocław, PolandInhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel <i>N</i>-substituted 1<i>H</i>-pyrrolo[3–c]pyridine-1,3(2<i>H</i>)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC<sub>50</sub> value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E–BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force.https://www.mdpi.com/1420-3049/25/12/2934pyrrolo-pyridine derivativescyclooxygenaseanti-inflammatoryserum albumin interactionsfluorescence quenchingmolecular docking |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Edward Krzyżak Dominika Szkatuła Benita Wiatrak Tomasz Gębarowski Aleksandra Marciniak |
| spellingShingle |
Edward Krzyżak Dominika Szkatuła Benita Wiatrak Tomasz Gębarowski Aleksandra Marciniak Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives Molecules pyrrolo-pyridine derivatives cyclooxygenase anti-inflammatory serum albumin interactions fluorescence quenching molecular docking |
| author_facet |
Edward Krzyżak Dominika Szkatuła Benita Wiatrak Tomasz Gębarowski Aleksandra Marciniak |
| author_sort |
Edward Krzyżak |
| title |
Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives |
| title_short |
Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives |
| title_full |
Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives |
| title_fullStr |
Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives |
| title_full_unstemmed |
Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of <i>N</i>-substituted 1<i>H</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2H</i>)-diones Derivatives |
| title_sort |
synthesis, cyclooxygenases inhibition activities and interactions with bsa of <i>n</i>-substituted 1<i>h</i>-pyrrolo[3,4-c]pyridine-1,3(<i>2h</i>)-diones derivatives |
| publisher |
MDPI AG |
| series |
Molecules |
| issn |
1420-3049 |
| publishDate |
2020-06-01 |
| description |
Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel <i>N</i>-substituted 1<i>H</i>-pyrrolo[3–c]pyridine-1,3(2<i>H</i>)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC<sub>50</sub> value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E–BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force. |
| topic |
pyrrolo-pyridine derivatives cyclooxygenase anti-inflammatory serum albumin interactions fluorescence quenching molecular docking |
| url |
https://www.mdpi.com/1420-3049/25/12/2934 |
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