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.

Keywords: Multidrug resistance, Anticancer, Tetrahydroisoquinoline, Solubility, P-glycoprotein, THIQ, cytotoxicity, Qingdao, humidified atmosphere