Molecular docking and fluorescence characterization of benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives, a novel class of selective cyclooxygenase-2 inhibitors.
The aims of this study were: (i) to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 1-11; and (ii) to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their progression. Therefore, to know the precise mechanism by which these compounds interact with cyclooxygenase (COX)-2 enzyme, a molecular docking study was carried out; to assess spectroscopic characteristics, their absorption and emission properties were determined. The results demonstrated that some derivatives of benzothieno[3,2-d] pyrimidine exhibit interesting anti-inflammatory properties related to interactions with active sites of COX-2 and are fluorescent. The antipyrine-bearing compound 4 displayed high COX-2 affinity (ΔG = -9.4) and good fluorescent properties (Φfl = 0.032). Thus, some members of this new class of anti-inflammatory may be promising for fluorescence imaging of cancer cells that express the COX-2 enzyme. Further in vitro and in vivo studies are needed to confirm this hypothesis.
Department of Pharmaceuticals Sciences, University of Catania, V.le A. Doria 6, Catania 95125, Italy. mariarita.barone@libero.it.
Mariarita
M
Barone
Department of Bio-medical Sciences, Section of Physiology, University of Catania, V.le A. Doria 6, Catania 95125, Italy. giopannuzzo@interfree.it.
Giovanna
G
Pannuzzo
Department of Pharmaceuticals Sciences, University of Catania, V.le A. Doria 6, Catania 95125, Italy. asantaga@unict.it.
Andrea
A
Santagati
Department of Chemical Science, Section of Photochemistry, University of Catania, V.le A. Doria 6, Catania 95125, Italy. acatalfo@unict.it.
Alfio
A
Catalfo
Department of Chemical Science, Section of Photochemistry, University of Catania, V.le A. Doria 6, Catania 95125, Italy. gdeguidi@unict.it.
Guido
G
De Guidi
Department of Bio-medical Sciences, Section of Physiology, University of Catania, V.le A. Doria 6, Catania 95125, Italy. cardile@unict.it.
Venera
V
Cardile
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000737:chemistry; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D051546:Cyclooxygenase 2