Síntese e avaliação da atividade anti-inflamatória de um novo análogo isoxazólico baseado no celecoxibe e neolignanas

Abstract

Anti-inflammatory drugs can lead to significant adverse reactions, such as gastric lesions, renal, and cardiovascular complications. Therefore, the search for novel alternatives to treat inflammatory diseases is critical. This study aimed to synthesize and investigate the effects of a new hybrid isoxazolic analog based on the structure of celecoxib and neolignans (LASQUIM-PC-1) on mechanical hyperalgesia and edema formation in the acute inflammatory response induced by carrageenan (Cg). The synthesis involved coupling 4-ethynylbenzenesulfonamide with a chloro-oxime through a [3+2] cycloaddition reaction, and the compound was characterized by proton nuclear magnetic resonance (1H-NMR). Male Swiss mice were treated with LASQUIM-PC-1 (1, 3, or 10 mg/kg, orally), celecoxib (10 mg/kg, reference drug), or vehicle (1% DMSO solution) (n = 5-7 animals/group), 1 hour before intraplantar injection of Cg (300 μg/paw) into the right hind paw. The contralateral paw received a 0.9% saline solution injection. Edema formation was determined by the volume difference between the right and left paws using a digital plethysmometer at 0.5, 1, 2, and 4 hours after Cg injection. Mechanical hyperalgesia was evaluated using a digital analgesimeter (Von Frey) as a pressure transducer, recording the force applied until paw withdrawal at 3 and 4 hours post-Cg injection. Oral treatment with LASQUIM-PC-1 at doses of 3 and 10 mg/kg reduced edema formation at all time points compared to the control group. Celecoxib reduced edema formation at 1, 2, and 4 hours. Treatment with LASQUIM-PC-1 at 10 mg/kg and celecoxib reduced mechanical hyperalgesia at all evaluated time points.