Synthesis, in vitro and in silico studies of HO-1 inducers and lung antifibrotic agents.
Valeria PittalàLuca VanellaChiara Bianca Maria PlataniaLoredana SalernoMarco RaffaeleEmanuele AmataAgostino MarrazzoGiuseppe FlorestaGiuseppe RomeoKhaled GreishSebastiano IntagliataClaudio BucoloValeria SorrentiPublished in: Future medicinal chemistry (2020)
Aim: Dimethyl fumarate (DMF) analogs were synthesized to obtain inducers of HO-1 and antifibrotic agents. Methods: HO-1 expression levels were measured on lung fibroblasts (MRC5). NMR and docking studies were performed. Heme oxygenase activity, gene levels and protein expression have been measured for the most active compound 1a. Collagen production by fibroblast after exposure to TGF-β was measured. Results: Compound 1a showed to be a strong HO-1 inducer. Its activity seems to be mediated by activation of nuclear factor erythroid 2 related factor 2 (Nrf2). TGF-β-induced collagen production was significantly decreased on MRC5, pretreated with DMF or 1a. DMF and 1a have a high potential for treatment of lung fibrotic injuries.
Keyphrases
- nuclear factor
- pi k akt
- toll like receptor
- transforming growth factor
- molecular docking
- magnetic resonance
- poor prognosis
- wound healing
- case control
- oxidative stress
- molecular dynamics
- high resolution
- drug induced
- signaling pathway
- diabetic rats
- idiopathic pulmonary fibrosis
- mass spectrometry
- extracellular matrix
- long non coding rna
- dna methylation
- risk assessment
- human health
- combination therapy
- endothelial cells
- protein protein
- epithelial mesenchymal transition
- small molecule
- climate change