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This study was conducted to investigate putative antagonism of integrin receptors αMβ2 and αLβ2 by a novel coumarin derivative (BOL-303225-A), its efficacy in-vivo after retinal ischaemia–reperfusion injury, and its bioavailability in rat plasma. A cellular adhesion assay in Jurkat and U937 cells, and a flow cytometry assay with an antibody against the β2 subunit were conducted. BOL-303225-A bioavailability in rat plasma and the retinal levels of myeloperoxidase (MPO) after ischaemia–reperfusion injury were evaluated after oral administration (10 mg kg−1). In-vitro cell viability assays revealed no cytotoxicity for BOL-303225-A over a wide dose range, and IC50 values of 32.3 ± 1.5 μM and 84.95 ± 2.3 μM were found for Jurkat and U937 cells, respectively. The drug showed specific binding to the αMβ2 and αLβ2 integrin receptors expressed by U937 and Jurkat cells, respectively, producing a fluorescence shift towards lower values in a concentration-dependent manner. The pharmacokinetic profile of BOL-303225-A exhibited rapid absorption following oral administration in the rat. A significant reduction of retinal MPO levels was observed in drug-treated rats. This study demonstrated that BOL-303225-A acts as an antagonist of the integrin αLβ2 and αMβ2 receptors, suggesting that this drug could be used for ocular diseases such as diabetic retinopathy. [ABSTRACT FROM AUTHOR]

: Objectives This study was conducted to evaluate the anti-inflammatory effects of besifloxacin, a novel fluoroquinolone under clinical evaluation for treatment of ophthalmic infections. : Methods Cytokine expression in human THP-1 monocytes was stimulated by lipopolysaccharide (LPS), and Luminex technology was used to determine the effect of besifloxacin on LPS-induced cytokine expression. Moxifloxacin, a marketed fluoroquinolone used in ophthalmic infections, was used as the control. : Results LPS induced measurable cytokine expression for 14 of the 16 cytokines assayed. Besifloxacin significantly inhibited LPS-stimulated cytokine production in a dose-dependent manner, with a comparable [granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1β, IL-8, interferon-inducible protein (IP-10), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α)] or better [granulocyte CSF (G-CSF), IL-1α, IL-1 receptor antagonist (IL-1ra) and IL-6] potency compared with moxifloxacin. A significant inhibitory effect of besifloxacin was observed at 0.1 mg/L for IL-1α, at 1 mg/L for G-CSF, IL-1ra and IL-6 and at 30 mg/L for GM-CSF, IL-12p40, IL-1β, IL-8, IP-10, MCP-1 and MIP-1α. : Conclusions Besifloxacin acts as an anti-inflammatory agent in monocytes in vitro; this attribute may enhance its efficacy in ocular infections with an inflammatory component and warrants further investigation. [ABSTRACT FROM AUTHOR]