Studies on anthracenes. 2. Synthesis and cytotoxic evaluation of 9-acyloxy1,8-dichloroanthracene derivatives

The synthesis and cytotoxic evaluation of 9-acyloxy 1,8-dichloroanthracene derivatives are described. The system selectively reduces the carbonyl grou p flanked by the peri substituents of the anthracenediones to give the corr esponding 1,8-dichloro-9(10H)-anthracenone. Simple acylation of anthracenon e occurred with appropriate acyl chlorides in CH,CI, with a catalytic amoun t of pyridine to give the 9-acyloxy-1,8-dichloroanthracene derivatives. Con siderable interest has developed in the mechanism of how anthracenones achi eve this desirable selectivity. These compounds were evaluated in vitro for their ability to inhibit the growth of human oral epidermoid carcinoma cel ls (KB cell line), human cervical carcinoma cells of ME 180 (GBM 8401) and Chinese hamster ovary (CHO) cells, respectively, as compared to mitoxantron e. The in vitro cytotoxicity evaluation of 9-acyloxy 1,8-dichloroanthracene s against these above cell lines revealed for most of the compounds a cytot oxic potency lower than that of mitoxantrone. The most active compounds wer e thus selected for further in vitro biological evaluation and structural m odification.