Derivatives of the new ring system indolo[1,2-c]benzo[1,2,3]triazine with potent antitumor and antimicrobial activity

Derivatives of the new ring system indolo[1,2-c]benzo[1,2,3]triazine 5 were synthesized by diazotization of substituted 2-(2-aminophenyl)indoles follo wed by an intramolecular coupling reaction of the diazonium group with the indole nitrogen. To obtain the indolobenzotriazine system it was necessary to protect the 3 position of the indole nucleus to avoid cyclization into t he indolo[3,2-c]cinnoline system 4. Indolobenzotriazines 5a-g were evaluate d in vitro for antitumor activity against a panel of leukemia-, lymphoma-, carcinoma-, and neuroblastoma-derived cell lines. Some compounds inhibited the proliferation of T and B cell lines at submicromolar concentrations, wh ereas their activity against solid tumor cell lines was in the micromolar r ange. When evaluated for their antifungal potential 5a,d inhibited some of the fungi tested, although at concentrations very close to those inhibiting the proliferation of human cells. On the contrary all indolobenzotriazines proved fairly potent and selective inhibitors of Streptococcus and Staphyl ococcus. In particular 5b,c,g were up to 80 times more potent than the refe rence drug streptomycin and inhibited the growth of the above Gram-positive bacteria at concentrations far lower than those cytotoxic for animal cells .