Next Article in Journal
Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models
Previous Article in Journal
From Seeds to Fibrils and Back: Fragmentation as an Overlooked Step in the Propagation of Prions and Prion-Like Proteins
Open AccessArticle

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

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
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ege University Bornova, 35100 Izmir, Turkey
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;
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
Show Figures

Figure 1

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.

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.

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.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop