Abstract
Coumarin and their derivatives have drawn much attention in the pharmacological and pharmaceutical fields due to their broad range and diverse biological activities. In the present work, starting from the 6-amino-7-hydroxy-4-methyl-2H-chromen-2-one, a series of 6-(substituted benzylamino)-7-hydroxy-4-methyl-2H-chromen-2-ones 1–11 was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. Compounds 2, 3, 4 and 9 showed significant (p < 0.001) reduction of rat paw edema volume after 1 h from the administration of the carrageenan compared to the reference drug, indomethacin. On the other hand, compounds 4 and 8 showed the highest anti-inflammatory activity, surpassing indomethacin after 3 h with 44.05% and 38.10% inhibition, respectively. Additionally, a molecular docking study was performed against the COX enzyme using the MOE 10.2010 software.
Highlights
Inflammation is a complex host response to tissue injury that is contolled by many mediators among which are the prostaglandins (PGs)
Molecules 2015, 20 arachidonic acid (AA). It exists in two isoforms, a constitutive form COX-1 that has a cytoprotective role in the gastrointestinal tract and an inducible form COX-2 which is responsible for the elevated production of PGs during inflammation
1–11 were synthesized in four steps (Scheme 1)
Summary
Inflammation is a complex host response to tissue injury that is contolled by many mediators among which are the prostaglandins (PGs). It exists in two isoforms, a constitutive form COX-1 that has a cytoprotective role in the gastrointestinal tract and an inducible form COX-2 which is responsible for the elevated production of PGs during inflammation. It has been already reported that coumarin is a potential nucleus for the development of anti-inflammatory drugs [6,7,8,9,10,11]. The anti-inflammatory effect of the newly synthesized compounds and a reference drug (indomethacin) was evaluated by the carrageenan-induced paw edema method [13]. NSAIDs like indomethacin interacts with the COX-2 enzyme by forming hydrogen bonds between a carboxylic acid and Arg120, a carbonyl oxygen with Ser530 and the OH of a carboxylic acid with Tyr355 [15]. Molecular docking was used to gain insight into the possible interactions of our newly synthesized compounds with the COX-1 and COX-2 enzymes
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