Indolo[2,3-b]quinoline derivatives as novel promising antitumor agents

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1 Pharmaceutical Research Institute, Warszawa, Mazovia, Poland
2 Faculty of Biotechnology, University of Michigan - Ann Arbor, Wrocław, Silesia, Poland
3 Faculty of Chemistry, University of St. Andrews, Wrocław, Silesia, Poland
4 Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
DOI
10.7287/peerj.preprints.1669v1
Published
Accepted
Subject Areas
Molecular Biology, Pharmacology
Keywords
indoloquinolines, cytotoxicity, topoisomerase II inhibitors, antitumor, MDR overcoming, SAR, selectivity
Copyright
© 2016 Kaczmarek et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ PrePrints) and either DOI or URL of the article must be cited.
Cite this article
Kaczmarek L, Badowska-Rosłonek K, Jaromin A, Łuniewski W, Peczyńska-Czoch W, Sidoryk K, Szczepek W, Wietrzyk J, Zagrodzki B. 2016. Indolo[2,3-b]quinoline derivatives as novel promising antitumor agents. PeerJ PrePrints 4:e1669v1

Abstract

In the search for novel antineoplastic compounds we have found that four-membered, linear 5,11-dimethyl -5H- indolo[2,3-b]quinoline (DIMIQ) reveals cytostatic activity in vitro and moderate antitumor activity in vivo in mice melanoma B16 as well as leukemias L1210 and P388. Preliminary studies showed that DIMIQ stabilizes DNA-topoisomerase II complex. Some years later indolo[2,3-b]quinoline was found as an alkaloid neocryptolepine in the West African shrub Cryptolepis sanguinolenta. Unfortunately, DIMIQ’s high toxicity, lack of selectivity and very low solubility in aqueous media seriously limit the practical use of this compound as an anticancer drug. Extensive research on the structure-activity relationships of different indolo[2,3-b]quinoline derivatives showed that the position and type of the substituent is conclusive both to the antitumor activity and general toxicity of the compound. These studies led us to discover derivatives of DIMIQ which exhibit very low toxicity against normal cells and are highly toxic against selected human tumors. These derivatives are soluble in water and some of them are able to overcome multidrug resistance in human tumors cells.

Author Comment

This is an Abstract submitted to the X MKNoL conference.