Synthesis of Variously Substituted 3-Phenoxymethyl Quinoxalin-2-Ones and Quinoxalines Capable to Potentiate In Vitro the Antiproliferative Activity of Anticancer Drugs in Multi-Drug Resistant Cell Lines

Roberta      Loddo; Paolo   La   Colla; Bernardetta      Busonera; Gabriella      Collu; Giuseppe      Paglietti; Sandra      Piras; Antonio      Carta; Mario      Loriga

Abstract

Two series of 1,6-dimethyl-3-phenoxymethylquinoxalin-2-ones and 1-benzyl-3-phenoxymethyl-7- trifluoromethylquinoxalin-2-ones, and a series of 2-benzyloxy-3-phenoxymethyl-7-trifluoromethylquinoxaline were synthesized. Their capability to restore/potentiate the antiproliferative activity of clinically useful drugs, such as doxorubicin (Doxo), vincristine (VCR) and etoposide (VP16), in drug-resistant human nasopharyngeal carcinoma KB cells (KBWT, KBMDR, KB7Dand KBV20C) was evaluated. In vitro data show that many quinoxalin-2-ones and quinoxalines potentiate the antiproliferative activity of Doxo and VCR in tumor-derived MDR cell lines. In this series, 17a turned out to be the most potent quinoxaline derivative in potentiating the antiproliferative activity of doxorubicin and vincristine against KBMDR and KBV20C resistant cell lines, respectively.

Keywords: etoposide, vincristine, doxorubicin, P-glycoprotein inhibitors, multidrug resistance, antiproliferative activity, quinoxalines, 2-Quinoxalinones