118762-04-2Relevant academic research and scientific papers
Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with PotentIn VitroAntiproliferative Activity
Fallica, Antonino N.,Sorrenti, Valeria,D’Amico, Agata G.,Salerno, Loredana,Romeo, Giuseppe,Intagliata, Sebastiano,Consoli, Valeria,Floresta, Giuseppe,Rescifina, Antonio,D’Agata, Velia,Vanella, Luca,Pittalà, Valeria
, p. 13373 - 13393 (2021/09/20)
Heme oxygenase-1 (HO-1) promotes heme catabolism exercising cytoprotective roles in normal and cancer cells. Herein, we report the design, synthesis, molecular modeling, and biological evaluation of novel HO-1 inhibitors. Specifically, an amide linker in the central spacer and an imidazole were fixed, and the hydrophobic moiety required by the pharmacophore was largely modified. In many tumors, overexpression of HO-1 correlates with poor prognosis and chemoresistance, suggesting the inhibition of HO-1 as a possible antitumor strategy. Accordingly, compounds7iand7l-pemerged for their potency against HO-1 and were investigated for their anticancer activity against prostate (DU145), lung (A549), and glioblastoma (U87MG, A172) cancer cells. The selected compounds showed the best activity toward U87MG cells. Compound7lwas further investigated for its in-cell enzymatic HO-1 activity, expression levels, and effects on cell invasion and vascular endothelial growth factor (VEGF) extracellular release. The obtained data suggest that7lcan reduce cell invasivity acting through modulation of HO-1 expression.
THERAPEUTIC METHODS
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Page/Page column 44; 45, (2013/06/27)
The present invention relates to methods of treatment of diseases mediated by ROR?.
COMPOUNDS AND METHODS
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Page/Page column 51, (2013/03/26)
The present invention relates to novel retinoid-reiated orphan receptor gamma (RORy) modulators and their use in the treatment of diseases mediated by RORy.
