Abstract
A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C4′-OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action.
Highlights
The inflammatory process consists of a physiological response triggered by a lesion or tissue infection and is characterized by a set of symptoms such as pain, edema, and redness in the affected region
We described the synthesis of a novel series of benzophenone derivatives attached to a thiazole group, two known pharmacophores which were potentially anti-inflammatory
In order to evaluate anti-inflammatory potential of the planned compounds, docked order to evaluate thethe anti-inflammatory potential of the planned compounds, theythey werewere docked into into the active of COX-1 and Thedocking dockingstudies studies were were performed performed using the active sitessites of COX-1 and whilewhile calculating the predicted binding affinity
Summary
The inflammatory process consists of a physiological response triggered by a lesion or tissue infection and is characterized by a set of symptoms such as pain, edema, and redness in the affected region. Inflammatory chemical mediators lead to increased vascular permeability and chemotaxis to the lesion site [1]. The treatment of inflammation is commonly based on the administration of non-steroidal anti-inflammatory drugs (NSAIDs) [2]. This class of drugs basically acts by inhibiting the isoforms of the enzyme cyclooxygenase: COX-1 and/or COX-2. Highly selective COX-2 anti-inflammatory drugs are associated with the development of thrombotic events since the selective inhibition of cyclooxygenase isoform 2 inhibits the synthesis of prostacyclin, which is an inhibitor of platelet aggregation. The activity of thromboxane produced via COX-1 becomes exacerbated, leading to increased platelet aggregation [2,4,5]
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