NOVEL INDENOISOQUINOLINES AS ANTINEOPLASTIC AGENTS

摘要

A number of indenoisoquinolines were prepared and evaluated for cytotoxicity in human cancer cell cultures and for activity vs. topoisomerase I. The two most cytotoxic indenoisoquinolines proved to be cis-6-ethyl-5, 6, 12, 13-tetrahydro-2, 3-dimethoxy-8, 9(methylenedioxy)-5, 11-dioxo-11H -indeno[1,2-c] isoquinoline and cis-6-allyl-5, 6, 12, 13-tetrahydro-2, 3-dimethoxy-8, 9-(methylenedioxy)-5, 11-dioxo-(11H)indeno[1,2-c] isoquinoline. Two of the most potent topoisomerase I inhibitors were 6-(3-carboxy-1-propyl)-5, 6-dihydro-5, 1 Idioxo-11H-indeno[ 1,2-c] isoquinoline (26) and 6-ethyl-2, 3-dimethoxy-8, 9-(methylenedioxy)11H-indeno[ 1,2-c]isoquinolinium chloride (27). Two additional potent topoisomerase I inhibitors, 6-allyl-5, 6-dihydro-2, 3-dimethoxy-8, 9-(methylenedioxy)-5, 11-dioxo-11H-indeno[1,2-c] isoquinoline (13c) and 5, 6-dihydro-6-(4-hydroxybut-1-yl)-2, 3-dimethoxy-8, 9-methylenedioxy-5, 11 dioxo-(11H)indeno[1, 2-c]isoquinoline (19a), did not unwind DNA and did not affect topoisomerase II.