THOXY-5,6,11-TRIMETHYL-6H-INDOLO[2,3-B]QUINOLINIUM AND THYL-5,6,11-TRIMETHYL-6H-INDOLO[2,3-B]QUINOLINIUM, THOXY-5,6,11-TRIMETHYL-6H-INDOLO[2,3-B]QUINOLINIUM DERIVATIVES AS NOVEL CYTOTOXIC AGENTS AND DNA TOPOISOMERASE-II INHIBITORS

New members of the cytotoxic indolo[2,3-b]quinoline family, with a met hyl groups at N-5, N-6 (their presence stabilizes the positive charge of the molecule), were prepared using a modified Graebe-Ullmann reacti on. The derivatives obtained were well soluble in water in a non-pH-de pendent manner. They displayed strong antimicrobial activity against G ram-positive bacteria and pathogenic fungi (the MIC values fall betwee n 0.0025 and 0.12 mM) and highly selective cytotoxicity in vitro again st different human cancer cell lines: colon adenocarcinoma SW 707 lung carcinoma A 549, transitional cell carcinoma Hu 1703, and oral epider moid carcinoma KB, in the range of 0.01 to 3.0 mu M. They also stimula ted the formation of topoisomerase-ll-mediated DNA cleavage at concent ration from 0.04 to 0.5 mu M. These observations correspond well with the ability of the tested compounds to increase the melting temperatur e of calf thymus DNA (Delta T-m being between 13 degrees C and 22 degr ees C).