Discovery of tropinone-thiazole derivatives as potent caspase 3/7 activators, and noncompetitive tyrosinase inhibitors with high antiproliferative activity: Rational design, one-pot tricomponent synthesis, and lipophilicity determination.


Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089, Bydgoszcz, Poland. Electronic address: [Email]


We have designed novel tropinone-thiazole derivatives that showed high antiproliferative activity against a variety of cancer cell lines via caspase 3/7 activation mechanism. Among the derivatives, compounds 3b-3h were found to exhibit high activity against human leukemia (MV4-11), human lung carcinoma (A549), human breast carcinoma (MCF-7), and skin melanoma (B16-F10) cancer cell lines, with IC50 values of 5.43-11.06 μM. The lead compound 3g increases caspase 3/7 activity in A549 cells 25 times more than the control, and 2 times more than reference drug camptothecin. We have also found that tropinone-thiazole derivatives exhibit high tyrosinase inhibitory activity. The lead compounds 3g and 3h showed tyrosinase inhibition effect, with IC50 values 3.22 and 3.51 μM, respectively. These inhibitory activities are 22 times higher than the activity of kojic acid (IC50 72.27 μM) and 120 times higher than activity of ascorbic acid (IC50 386.5 μM). For compounds 3g and 3h, the experimentally determined lipophilicity correlates very well with their enzymatic activities. These data suggest that presented compounds could constitute lead anticancer drug candidates.


Antiproliferative activity,Caspase,Mushroom tyrosinase,Thiazole,Tropinone,

OUR Recent Articles