Synthesis, antiproliferative activity and autophagic flux inhibition of new arylsparteine derivatives

New series of arylsparteine derivatives were synthesized and evaluated for their cytotoxic activity against four human cancer cell lines (cervical epithelial carcinoma cells Hela, breast cancer cells MCF-7, lung cancer cells A549, and glioma cells U87 MG) and one normal fibroblast cell line. Structure-activity relationship revealed that introduction of 4-quinolinyl moiety to sparteine afforded a hybrid compound 10 with considerable antiproliferative activity against all tested cancer cell lines. Compound 10, the most active agent in this study possessed IC50 values of 5.97 +/- 1.1 and 9.52 +/- 0.3 mu M against A549 and Hela cancer cell lines, respectively. Inhibition of autophagic flux proved to be the underlying mechanism for the antiproliferative activity of 10 which was further validated by decreased levels of ATP in cancer cells treated with 10. In addition, co-treatment of 10 and rapamycin restored cell viability which comes in good agreement with the proposed autophagic flux inhibition for 10.