Nitric oxide is an important inflammation mediator with a recognized role in the development of different cancers. Gliomas are primary tumors of the central nervous system with poor prognosis, and the expression of the inducible nitric oxide synthase correlates with the degree of malignancy, changes in vascular reactivity, and neo-angiogenesis. Therefore, targeting the nitric oxide biosynthesis appears as a potential strategy to impair glioma progression. In the present work a set of aryl and amido-aryl acetamidine derivatives were synthesized to obtain new potent and selective inducible nitric oxide synthase inhibitors with improved physicochemical parameters with respect to the previously published molecules. Compound 17 emerged as the most promising inhibitor and was evaluated on C6 rat glioma cell line, showing antiproliferative effects and high selectivity over astrocytes.

Antiglioma Activity of Aryl and Amido-Aryl Acetamidine Derivatives Targeting iNOS: Synthesis and Biological Evaluation

Maccallini, Cristina
;
Gallorini, Marialucia;Amoia, Pasquale;Ammazzalorso, Alessandra;De Filippis, Barbara;Fantacuzzi, Marialuigia;Giampietro, Letizia;Cataldi, Amelia;Amoroso, Rosa
2020

Abstract

Nitric oxide is an important inflammation mediator with a recognized role in the development of different cancers. Gliomas are primary tumors of the central nervous system with poor prognosis, and the expression of the inducible nitric oxide synthase correlates with the degree of malignancy, changes in vascular reactivity, and neo-angiogenesis. Therefore, targeting the nitric oxide biosynthesis appears as a potential strategy to impair glioma progression. In the present work a set of aryl and amido-aryl acetamidine derivatives were synthesized to obtain new potent and selective inducible nitric oxide synthase inhibitors with improved physicochemical parameters with respect to the previously published molecules. Compound 17 emerged as the most promising inhibitor and was evaluated on C6 rat glioma cell line, showing antiproliferative effects and high selectivity over astrocytes.
File in questo prodotto:
File Dimensione Formato  
acsmedchemlett.0c00285 (1).pdf

accesso aperto

Descrizione: Article
Tipologia: PDF editoriale
Dimensione 1.39 MB
Formato Adobe PDF
1.39 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/724826
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact