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-li nked and N-linked substituents in the 10-position are described. Previous s tudies have shown that 9-acyloxy 1,5-dichloroanthracenes and 9-acyloxy 1,8- dichloroanthracenes displayed a potential cytotoxic effect. These results h ave encouraged us in further investigation of potential anthracenone deriva tives. Therefore, a series of 10-substituted 1,8-dichloro-9(10H)-anthraceno ne derivatives were synthesized. These compounds were evaluated for their a bility to inhibit the growth of human oral epidermoid carcinoma cells (KB c ell 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, resp ectively. In addition, redox property of the compounds for the inhibition o f lipid peroxidation in model membranes was determined. Compounds 4b and 4d exhibited stronger antioxidant activity than ascorbic acid, (+)-alpha -toc opherol and mitoxantrone, respectively.