Abstract

1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) represents an excellent lead candidate for therapeutic and/or diagnostic applications in oncology. However, because its utility is limited by its relatively high degree of lipophilicity, novel analogues of 1 with reduced lipophilic character were designed by substituting methylene groups with more polar functional groups in the propylene linker and at the tetralin C4 position. For the chiral analogues, separate enantiomers exhibited substantial and roughly equal affinities within a given receptor subtype, with the greatest difference observed for compound 9 at σ1 (7.5-fold; (-)-(S)-9 Ki=94.6 nM, (þ)-(R)-9 Ki=12.6 nM). Compound (-)-(S)-9 was also found to be the most σ2-selective agent (σ2 Ki=5.92 nM), to possess a lipophilicity consistent with entry into tumor cells (log D7.4 = 2.38), and to show minimal antiproliferative activity. However, (-)-(S)-9 exhibited moderate activity (EC50= 8.1 μM) at the P-gp efflux pump.

Autore Pugliese

• Abate Carmen , Lacivita Enza , Niso Mauro

Tutti gli autori

• ABATE C.;LACIVITA E.;NISO M.;PERRONE R.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2011

ISSN

0022-2623

ISBN

Non Disponibile

Numero di citazioni Wos

21

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

20

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile