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Mono substituted 5H- and 6H-indolo[2,3-b]quinoline derivatives and their ability to overcome the barrier of drug resistance.

Wojciech Łuniewski 1Bogdan Zagrodzki 1Marta Świtalska 2Paulina Ćwiek 2Joanna Godlewska 2Joanna Wietrzyk 1Łukasz S. Kaczmarek 2Wanda Peczyńska-Czoch 3

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
2. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland
3. Wrocław University of Technology, Department of Organic Chemistry, Wybrzeże Wyspiańskiego 27, Wrocław 50-370, Poland

Abstract

A series of novel 5-H- and 6H- indolo[2,3-b]quinoline derivatives bearing (dialkylamino)alkyl chains at C-2 or C-9 position attached to indoloquinoline core via amine, amide or ether bond were prepared and tested for ability to break multidrug resistance in cancer cells.

In our research we studied the cytotoxic activity of tested compounds on three various human cancer cell lines and their drug-resistant sublines: human colon cancer (LoVo) and doxorubicin-resistant LoVo/DX (P-gp-dependent, MRP-, LRP-dependent multidrug resistance), uterine sarcoma (MES-SA) and MES-SA/DX5 (P-gp-dependent resistance to doxorubicin), human promyelocytic leukemia cell line (HL-60) and HL-60/MX2 (P-gp-independent and topoisomerase II-dependent resistance).

The results of our investigations showed that all these compounds were able to overcome the barrier of drug resistance. The compounds of this group had the highest activity against leukemia cell line. Only three compounds did not show ability to overcome the barrier of drug resistance against human colon cancer (ISS-22 and ISS-103) and uterine sarcoma cell line (ISS-22 and IQ6/9/2). However, against leukemia cell line the ability to overcome this barrier, was similar to other compounds. The most effective derivatives of the all 5-H indoloquinolines tested were ISS-104 (C-2) and ISS-89 (C-9) those which were connected with indoloquinoline core via amine bond. In series 6H- indoloquinolines the most effective derivatives were ISS-43 (C-2) and ISS-26 (C-9) which were connected with indoloquinoline core also via amine bond.

 

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Presentation: Poster at VI Multidyscyplinarna Konferencja Nauki o Leku, by Wojciech Łuniewski
See On-line Journal of VI Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2008-04-07 13:11
Revised:   2009-06-07 00:48