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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

Effects of Acylhydrazone Derivatives on Experimental Pulmonary Inflammation by Chemical Sensitization

Author(s): Katharina Rodrigues de Lima Porto Ramos, Sandra Cabral da Silva, Pascal Marchand, Fernanda Virgínia Barreto Mota, Julyanne Cunha de Assis Correia, Jéssica de Andrade Gomes Silva, George Torres de Lima, Marllon Alex Santana, Willian Charles da Silva Moura, Vanda Lúcia dos Santos, Ricardo Olímpio Moura and Teresinha Gonçalves da Silva*

Volume 21, Issue 2, 2022

Published on: 29 August, 2022

Page: [135 - 151] Pages: 17

DOI: 10.2174/1871523021666220729141608

Price: $65

Abstract

Background: Chronic lung diseases are characterized by airway inflammation and remodelling of the lung parenchyma that triggers considerable impairment of respiratory function.

Objective: In this study, two compounds belonging to the N-acylhydrazone class were evaluated, aiming to identify new therapeutic agents for pulmonary inflammatory diseases.

Materials and Methods: The acute toxicity of 2-cyano-N'-(3-ethoxy-4-hydroxybenzylidene)- acetohydrazide (JR-12) and N'-benzylidene-2-cyano-3-phenylacrylohydrazide (JR09-Bz) was evaluated. Afterwards, they were tested in models of ovalbumin (OVA)-induced allergic asthma and pleurisy, bleomycin-induced pulmonary fibrosis, in addition to mucolytic activity.

Results and Discussion: The compounds did not show toxicity at the dose of 2,000 mg/kg, and no animal died. On OVA-induced pleurisy, animals treated with JR-12 or JR09-Bz at a dose of 10 mg/kg (orally) showed significant inhibition of the leukocyte infiltrate in the bronchoalveolar lavage by 62.5% and 61.5%, respectively, compared to the control group. The compounds JR-12 and JR09-Bz were also active in blocking the allergic asthmatic response triggered by OVA, reducing the leukocyte infiltrate by 73.1% and 69.8%, respectively. Histopathological changes and mast cell migration in treated animals with JR-12 or JR09-Bz were similar to treatment with the reference drugs dexamethasone and montelukast. JR-12 and JR09-Bz also reversed airway remodeling in animals on the bleomycin-induced fibrosis model compared to the control group. Furthermore, it was observed that N-arylhydrazone derivatives showed expectorant and mucolytic activities, increasing mucus secretion by 45.6% and 63.8% for JR-12 and JR09-Bz, respectively.

Conclusion: Together, the results show that JR-12 and JR09-Bz showed promising activity against airway inflammation, as well as low toxicity.

Keywords: Remodeling, Asthma, cell migration, histopatology, pulmonary fibrosis, Acylhidrazone.

Graphical Abstract

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