4-(Phenylselanyl)-2H-chromen-2-one-Loaded Nanocapsule Suspension-A Promising Breakthrough in Pain Management: Comprehensive Molecular Docking, Formulation Design, and Toxicological and Pharmacological Assessments in Mice

4-(苯基硒基)-2H-色满-2-酮纳米胶囊悬浮液——疼痛管理的重大突破:全面的分子对接、配方设计以及小鼠毒理学和药理学评估

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作者:Caren Aline Ramson da Fonseca, Vinicius Costa Prado, Jaini Janke Paltian, Jean Carlo Kazmierczak, Ricardo Frederico Schumacher, Marcel Henrique Marcondes Sari, Larissa Marafiga Cordeiro, Aline Franzen da Silva, Felix Alexandre Antunes Soares, Robson da Silva Oliboni, Cristiane Luchese, Letícia Cruz,

Abstract

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients' quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa β. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.

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