Studies on anthracenes. 3. Synthesis, lipid peroxidation and cytotoxic evaluation of 10-substituted 1,5-dichloro-9(10H)-anthracenone derivatives

The synthesis of a series of 1,5-dichloro-9(10H)-anthracenones bearing O-linked and N-linked substituents in the 10-position are described. Previous studies have shown that 9-acyloxy 1,5-dichloroanthracenes and 9-acyloxy 1,8-dichloroanthracenes displayed a potential cytotoxic effect. These results have encouraged us in further investigation of potential anthracenone derivatives. Therefore, a series of 10-substituted 1,8-dichloro-9(10H)-anthracenone derivatives were synthesized. These compounds were evaluated for their ability to inhibit the growth of human oral epidermoid carcinoma cells (KB cell line), human cervical carcinoma cells of ME 180 (GBM 8401) and Chinese hamster ovary (CHO) cells, respectively. Compounds 3c and 4c of this series compare favorably in the KB cellular assay with mitoxantrone. Compound 4c showed combined inhibitory action against KB, GBM and CHO cell growth, respectively. In addition, redox property of the compounds for the inhibition of lipid peroxidation in model membranes was determined. Compounds 4b and 4d exhibited stronger antioxidant activity than ascorbic acid, (+)-α-tocopherol and mitoxantrone, respectively.