LASSBio-1586, an N-acylhydrazone derivative, attenuates nociceptive behavior and the inflammatory response in mice.

Juliane Cabral Silva,Lídia Moreira Lima,Sarah Raquel Gomes De Lima-Saraiva,Jackson Roberto Guedes Da Silva Almeida,Edilson Beserra De Alencar Filho,Rosemairy Luciane Mendes,Eliezer Jesus De Lacerda Barreiro,Mariana Gama E Silva,Tâmara Coimbra Diniz,Érica Martins De Lavor,Juliana Mikaelly Dias Soares,Raimundo Gonçalves De Oliveira Júnior,Gautam Sethi

doi:10.1371/journal.pone.0199009

Abstract

Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Highlights

Pain is one of the most serious societal problems; it limits productivity and reduces quality of life as well as has high social and economic impacts
LASSBio-1586 was shown to inhibit microtubule polymerization, demonstrating a broad in vitro and in vivo antiproliferative profile with satisfactory selectivity for cancer cells [7]. In this sense and following the principle of drug repurposing, we describe in this paper the antinociceptive and anti-inflammatory potential of LASSBio-1586 in various experimental models
It is not possible to specify the nociceptive pathways in which the molecule acts

Summary

Introduction

Pain is one of the most serious societal problems; it limits productivity and reduces quality of life as well as has high social and economic impacts. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Methods

Results

Conclusion