Synthetic Inhibitors of DNA Topoisomerase I and II

• Published in: Chemical & pharmaceutical bulletin Vol. 47; no. 1; pp. 48 - 53
• Main Authors: KATAYAMA, Hajime, KAWADA, Yusuke, KANEKO, Kimiyoshi, OSHIYAMA, Takamitsu, TAKATSU, Noriyuki
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1999; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; antitumor activity; Biological and medical sciences; cytotoxicity; DNA topoisomerase (ATP-hydrolysing) inhibitors; DNA topoisomerase I; DNA topoisomerase II; DNA topoisomerase inhibitors; DNA, Superhelical - chemistry; DNA, Superhelical - metabolism; dual inhibitor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; General aspects; Indoles - chemical synthesis; Indoles - pharmacology; Leukemia P388 - drug therapy; Leukemia P388 - enzymology; Male; Medical sciences; Mice; Mice, Inbred Strains; Nuclear Magnetic Resonance, Biomolecular; Pharmacology. Drug treatments; pyrazolo[1, 5-a]indole; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Antineoplastic agent; Organic cation; Angular nitrogen heterocycle; Cytotoxicity; Hydrazinium compounds; Isomerases; Structure activity relation; Aromatic compound; Chemical synthesis; Tumor cell; DNA topoisomerase (ATP-hydrolysing); Enzyme; Rodentia; DNA topoisomerase; Enzyme inhibitor; Tricyclic compound; In vitro; In vivo; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Cell line; Treatment; Mouse; Animal; Tertiary amine
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.47.48

A new type of synthetic inhibitor of DNA topoisomerase I and II was examined and several of these derivatives exhibited strong dual activity against these enzymes. This series of compounds showed high cytotoxic activities against cancer cells, but only a limited number of compounds showed any noticeable activity in an in vivo test against murine P388. Non-specific toxicity was observed in the in vivo tests.