SYNTHESIS, ANTITUMOR EVALUATION AND SAR OF NEW 1H-PYRROLO [3,2-C] QUINOLINE-6,9-DIONES AND 11H-INDOLO [3,2-C] QUINOLINE-1,4-DIONES

New 1H-pyrrolo [3,2-c] quinoline-6,9-diones, 11H-indolo [3,2-c] quinol ine-1,4-diones and 7,8,9,10-tetrahydro-11H-indolo [3,2-c] quinoline-1, 4-diones, either unsubstituted or methylated, have been synthesized an d evaluated for antitumor activity. They were compared to previously d escribed quinones which bear either a methoxy group or an aziridinyl s ubstituent on the quinone nucleus in order to establish structure-acti vity relationships and to obtain compounds as active as aziridinyl-qui nones, but with less toxicity. A new synthetic route was developed usi ng dimethoxy derivatives as key compounds that reacted with ceric ammo nium nitrate (CAN) to give quinones by oxidation demethylation. The bi ological results obtained in vitro indicated that: (i) new quinones di splay cytotoxicity higher than that of the methoxyquinones; (ii) unsub stituted compounds are the most active; (iii) methylation of the pyrro le NH has no influence on unsubstituted quinones, but affords inactive derivatives when the quinone nucleus is methylated; (iv) compared to the aziridinyl-quinones, some compounds are equally active or more act ive. Despite the cytotoxicity exerted in vitro, we could not find evid ence for any antitumor activity of quinones against in vivo P388 murin e leukemia.