Edward Krzyżak1, Dominika Szkatuła2, Benita Wiatrak3, Tomasz Gębarowski3, Aleksandra Marciniak1. 1. Department of Inorganic Chemistry, Wroclaw Medical University, ul. Borowska 211a, 50-556 Wrocław, Poland. 2. Department of Medicinal Chemistry, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland. 3. Department of Basic Medical Sciences, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Abstract
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 N-substituted 1H-pyrrolo[3-c]pyridine-1,3(2H)-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 IC50 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.
Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. n class="Gene">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 N-substituted 1H-pyrrolo[3-c]pyridine-1,3(2H)-dionesderivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 andCOX-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 andCOX-2 inhibitory studies revealed that all the compounds potentially inhibitedCOX-1 andCOX-2. The IC50 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.
Authors: Dominika Szkatuła; Edward Krzyżak; Szczepan Mogilski; Jacek Sapa; Barbara Filipek; Piotr Świątek Journal: Molecules Date: 2020-12-12 Impact factor: 4.411