Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator

Erika Nieddu, Benedetta Pollarolo, Marco T. Mazzei, Maria Anzaldi, Silvia Schenone, Nicoletta Pedemonte, Luis J V Galietta, Mauro Mazzei

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The phenylhydrazone RDR-1 is endowed with moderate activity as F508del-CFTR corrector; nevertheless, its simple structure enables stimulating developments in this class of correctors. Therefore, we synthesized a number of phenylhydrazones 3 by reacting phenylhydrazine derivatives 1 with furfural derivatives 2. By the same reaction, also the pyridine derivatives 4, the thiophene derivatives 5, and the hydrazides 6 and 7 were prepared. All compounds were tested as F508del-CFTR correctors in the cystic fibrosis (CF) bronchial epithelial cell line CFBE41o-, using corr-4a and VX-809 as controls. Some of the tested compounds emerged as interesting F508del-CFTR correctors at 20 μM (3c) and 2 μM (5d). 3c and 5d administered together with VX-809 produced a satisfactory additivity of action. When the structure of 5d was overlapped with RDR-1 and five other established correctors, a shared central design was clearly visible. This fact may be of interest in the search for new F508del-CFTR correctors. Starting from RDR-1, a known F508del-CFTR corrector, some phenylhydrazones were synthesized. Two new compounds (3c and 5d) showed encouraging activity and, when administered together with the corrector VX-809, gave an additivity of action. Overlapping the molecular design of 5d with RDR-1 and other known correctors revealed a common structural moiety, which may help in the search for new drugs against cystic fibrosis.

Original languageEnglish
Pages (from-to)112-123
Number of pages12
JournalArchiv der Pharmazie
Volume349
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Furaldehyde
Thiophenes
Epithelial Cells
Cell Line
Pharmaceutical Preparations
lumacaftor
phenylhydrazone

Keywords

  • CFTR
  • Correctors
  • Cystic fibrosis
  • Ion channels
  • Phenylhydrazones

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmaceutical Science

Cite this

Nieddu, E., Pollarolo, B., Mazzei, M. T., Anzaldi, M., Schenone, S., Pedemonte, N., ... Mazzei, M. (2016). Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator. Archiv der Pharmazie, 349(2), 112-123. https://doi.org/10.1002/ardp.201500352

Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator. / Nieddu, Erika; Pollarolo, Benedetta; Mazzei, Marco T.; Anzaldi, Maria; Schenone, Silvia; Pedemonte, Nicoletta; Galietta, Luis J V; Mazzei, Mauro.

In: Archiv der Pharmazie, Vol. 349, No. 2, 01.02.2016, p. 112-123.

Research output: Contribution to journalArticle

Nieddu, Erika ; Pollarolo, Benedetta ; Mazzei, Marco T. ; Anzaldi, Maria ; Schenone, Silvia ; Pedemonte, Nicoletta ; Galietta, Luis J V ; Mazzei, Mauro. / Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator. In: Archiv der Pharmazie. 2016 ; Vol. 349, No. 2. pp. 112-123.
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