Title:Evaluation of In-Vitro Multidrug Resistance Reversal Activities of HZ08 analogues with Improved Soluble Property
Volume: 10
Issue: 1
Author(s): Xiaobu Lan, Haiyan Lin, Chunlei Tang, Xiaoyun Zhu, Hai Qian, Wenlong Huang and Yunman Li
Affiliation:
Keywords:
Multidrug resistance, Anticancer, Tetrahydroisoquinoline, Solubility, P-glycoprotein, THIQ, cytotoxicity, Qingdao, humidified atmosphere
Abstract: To overcome solubility problem observed in early preclinical study with the potent multidrug resistance
reversing agent HZ08 which containing tetrahydroisoquinoline skeleton, we synthesized a series of HZ08 analogues with
improved soluble properties. Compounds 6f, 10c and 10f showed significant reversal activity with little cytotoxicity. The
median inhibitory concentration (IC50) values of adriamycin were reduced to 0.9 μM, 1.1 μM and 0.71 μM, respectively
and comparable to those of reference drug verapamil (1.1 μM) and lead compound HZ08 (0.8 μM) on K562/A02 cells.
The solubility of all newly synthesized compounds had been improved.
