Biological Evaluation of ω-(Dialkylamino)alkyl Derivatives of 6H-indolo[2,3-b]quinoline - Novel Cytotoxic DNA Topoisomerase II Inhibitors

A series of novel 6H-indolo[2,3-b]quinoline derivatives, substituted at C-2, C-9 or N-6 position with dialkyl(alkylamino)alkyl chains differing in the number of methylene groups, was prepared. These compounds were evaluated in vitro for their antimicrobial and cytotoxic activity against several cell...

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Published in:Anticancer research 2005-07, Vol.25 (4), p.2857
Main Authors: JOANNA GODLEWSKA, WOJCIECH LUNIEWSKI, BOGDAN ZAGRODZKI, LUKASZ KACZMAREK, ALEKSANDRA BIELAWSKA-POHL, DANUTA DUS, JOANNA WIETRZYK, ADAM OPOLSKI, MAGDALENA SIWKO, ANNA JAROMIN, ANNA JAKUBIAK, ARKADIUSZ KOZUBEK, WANDA PECZYNSKA-CZOCH
Format: Article
Language:English
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Summary:A series of novel 6H-indolo[2,3-b]quinoline derivatives, substituted at C-2, C-9 or N-6 position with dialkyl(alkylamino)alkyl chains differing in the number of methylene groups, was prepared. These compounds were evaluated in vitro for their antimicrobial and cytotoxic activity against several cell lines of different origin and tested for their ability to influence the cell cycle and inhibit topoisomerase II activity. Liphophilic and calf thymus DNA-binding properties of these compounds were also investigated. All the compounds tested inhibited the growth of Gram-positive bacteria and fungi at MIC values ranging between 0.25 and 1 mM. They also showed cytotoxic activity against KB (human cervix carcinoma) cells (ID 50 varied from 2.1 to 9.0 μM) and were able to overcome multidrug resistance in colorectal adenocarcinoma LoVo/DX, uterine sarcoma MES-SA/DX5 and promyelocytic leukemia HL-60/MX2 cells (the values of the resistance index RI fell between 0.54 and 2.4). The compounds induced G2M-phase cell cycle arrest in Jurkat T-cell leukemia cells, revealed DNA-binding properties and inhibited topoisomerase II activity.
ISSN:0250-7005
1791-7530