PT - JOURNAL ARTICLE AU - ABDERRAZZAK MERZOUKI AU - MICHAEL D. BUSCHMANN AU - MYRIAM JEAN AU - REBECCA S. YOUNG AU - SI LIAO AU - SUSANNAH GAL AU - ZUOMEI LI AU - STEVE N. SLILATY TI - Adva-27a, a Novel Podophyllotoxin Derivative Found to Be Effective against Multidrug Resistant Human Cancer Cells DP - 2012 Oct 01 TA - Anticancer Research PG - 4423--4432 VI - 32 IP - 10 4099 - http://ar.iiarjournals.org/content/32/10/4423.short 4100 - http://ar.iiarjournals.org/content/32/10/4423.full SO - Anticancer Res2012 Oct 01; 32 AB - Background/Aim: Multidrug resistance poses a serious challenge in cancer therapy. To address this problem, we designed and synthesized Adva-27a, a novel non-ester GEM-difluorinated C-glycoside derivative of podophyllotoxin. Materials and Methods: Adva-27a activity was evaluated in a variety of assays including inhibition of topoisomerase IIα, cytotoxic activity in drug-sensitive and drug-resistant cancer cell lines, metabolic stability in human liver microsomes and pharmacokinetic properties in rats. Results: Adva-27a exhibited dose-dependent human topoisomerase IIα inhibitory activity and dose-dependent growth inhibitory activity in several drug-sensitive and two multidrug-resistant cancer cell lines. In the multidrug-resistant cell lines, MCF-7/MDR (breast cancer) and H69AR (small-cell lung cancer), Adva-27a was significantly more potent than etoposide. The metabolic stability of Adva-27a in human liver microsomes and its pharmacokinetic properties in rats were better than those of etoposide. Conclusion: Our studies have identified Adva-27a as a novel topoisomerase II inhibitor with superior cytotoxic activity against multidrug-resistant human cancer cells and more desirable pharmacokinetic properties than etoposide.