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Open AccessArticle

Effects of New NSAID-CAI Hybrid Compounds in Inflammation and Lung Fibrosis

1
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Florence, Viale G. Pieraccini n. 6, 50139 Florence, Italy
2
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University Bornova, 35100 Izmir, Turkey
3
Department of NEUROFARBA, Pharmaceutical Science Section, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(9), 1307; https://doi.org/10.3390/biom10091307
Received: 12 August 2020 / Revised: 2 September 2020 / Accepted: 8 September 2020 / Published: 10 September 2020
Pulmonary fibrosis is a severe lung disease with progressive worsening of dyspnea, characterized by chronic inflammation and remodeling of lung parenchyma. Carbonic anhydrases are a family of zinc-metallo-enzymes that catalyze the reversible interconversion of carbon-dioxide and water to bicarbonate and protons. Carbonic Anhydrase Inhibitor (CAI) exhibited anti-inflammatory effects in animals with permanent-middle-cerebral artery occlusion, arthritis and neuropathic pain. The pharmacological profile of a new class of hybrid compounds constituted by a CAI connected to a Nonsteroidal-Anti-Inflammatory Drug (NSAID) was studied in the modulation of inflammation and fibrosis. In-vitro tests were performed to assess their effects on cyclo-oxygenase enzyme (COX)-1 and COX-2, namely inhibition of platelet aggregation and thromboxane B2 production in the human-platelet-rich plasma, and reduction of Prostaglandin-E2 production in lipopolysaccharide-treated-RAW-264.7 macrophage cell line. The activity of compound 3, one of the most active, was studied in a model of bleomycin-induced lung fibrosis in C57BL/6 mice. The hybrid compounds showed a higher potency in inhibiting PGE2 production, but not in modifying the platelet aggregation and the TXB2 production in comparison to the reference molecules, indicating an increased activity in COX-2 inhibition. In the in-vivo murine model, the compound 3 was more effective in decreasing inflammation, lung stiffness and oxidative stress in comparison to the reference drugs given alone or in association. In conclusion, these CAI-NSAID hybrid compounds are promising new anti-inflammatory drugs for the treatment of lung chronic inflammatory diseases. View Full-Text
Keywords: NSAIDs; CAI; inflammation; pulmonary fibrosis; COX-1; COX-2 NSAIDs; CAI; inflammation; pulmonary fibrosis; COX-1; COX-2
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MDPI and ACS Style

Lucarini, L.; Durante, M.; Sgambellone, S.; Lanzi, C.; Bigagli, E.; Akgul, O.; Masini, E.; Supuran, C.T.; Carta, F. Effects of New NSAID-CAI Hybrid Compounds in Inflammation and Lung Fibrosis. Biomolecules 2020, 10, 1307. https://doi.org/10.3390/biom10091307

AMA Style

Lucarini L, Durante M, Sgambellone S, Lanzi C, Bigagli E, Akgul O, Masini E, Supuran CT, Carta F. Effects of New NSAID-CAI Hybrid Compounds in Inflammation and Lung Fibrosis. Biomolecules. 2020; 10(9):1307. https://doi.org/10.3390/biom10091307

Chicago/Turabian Style

Lucarini, Laura; Durante, Mariaconcetta; Sgambellone, Silvia; Lanzi, Cecilia; Bigagli, Elisabetta; Akgul, Ozlem; Masini, Emanuela; Supuran, Claudiu T.; Carta, Fabrizio. 2020. "Effects of New NSAID-CAI Hybrid Compounds in Inflammation and Lung Fibrosis" Biomolecules 10, no. 9: 1307. https://doi.org/10.3390/biom10091307

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