β-Carbolinedione Derivatives as Topoisomerase I Inhibitors

• Published in: Archiv der Pharmazie (Weinheim) Vol. 332; no. 7; pp. 249 - 254
• Main Authors: Mahboobi, Siavosh, Eluwa, Stella, Kumar KC, Sunil, Koller, Markus, Störl, Karin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.07.1999; WILEY‐VCH Verlag GmbH; Wiley-VCH
• Subjects: Antineoplastic agents; Biological and medical sciences; Carbolines - chemical synthesis; Carbolines - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; General aspects; Medical sciences; microwave irradiation; Pharmacology. Drug treatments; Topoisomerase I inhibition; Topoisomerase I Inhibitors; β-carbolinedione derivatives; Antineoplastic agent; Enzyme; Nitrogen heterocycle; DNA topoisomerase; Enzyme inhibitor; Selectivity; Tetracyclic compound; In vitro; Pyrrolidine derivatives; Imide; Isomerases; Structure activity relation; Microwave irradiation; Aromatic compound; Piperazine derivatives; Chemical synthesis
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/(SICI)1521-4184(19997)332:7<249::AID-ARDP249>3.0.CO;2-F

Pyrrolo[3,4‐c]‐β‐carbolinedione dimers 5—14 were synthesized from furo[3,4‐c]‐β‐carbolinediones and diamines by solvent‐free TaCl5/silica catalyzed reaction under microwave irradiation. The inhibitory property of these target compounds, the starting materials 2, 31, 32, and the N‐alkylated pyrrolo[3,4‐c]‐β‐carbolinediones 16, 17, 20—30 was tested against the relaxation of supercoiled pRB322 DNA by calf thymus topoisomerases I and II. Some of these compounds, especially 7 and 23 proved to be selective inhibitors of topoisomerase I.