Abstract

Many new chemotherapeutic agents are under preclinical investigation and, despite efforts to more selectively target cancer cells, limitations such as toxicity and inherent resistance are often encountered. Therefore, alternative strategies are needed to treat cancer and overcome such limitations. We describe novel cyclohexylpiperazine derivatives, designed as mixed affinity ligands for sigma (s) receptors and human D8– D7 sterol isomerase (HSI) ligands, which also exhibit P-glycoprotein (P-gp) inhibitory activity, with the aim of exploiting the antiproliferative effects mediated by s and HSI sites while overcoming P-gp-mediated resistance. All of the compounds displayed high affinities for s receptors and HSI sites, P-gp inhibitory activity, and s2 receptor agonist antiproliferative activity. Antiproliferative activity was also tested in PC-3 cells to establish s1 and HSI contribution. Compound cis-11, which displayed the best antiproliferative and P-gp inhibitory activities, was coadministered with 0.1 mm doxorubicin in MDCK-MDR1 cells. Compound cis-11 caused 70% and 90% cell death when coadministered at 30 mm and 50 mm, respectively. When administered alone, cis-11 resulted in 50% cell death, demonstrating its single agent antitumor properties in a tumor cell line overexpressing P-gp.

Autore Pugliese

• Abate Carmen , Berardi Francesco , Contino Marialessandra , Niso Mauro , Colabufo Nicola Antonio , Ferorelli Savina

Tutti gli autori

• ABATE C.;BERARDI F.;CONTINO M.;NISO M.;COLABUFO N.A.;PERRONE R.;FERORELLI S.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2011

ISSN

1860-7179

ISBN

Non Disponibile

Numero di citazioni Wos

29

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

28

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile