2. Academic Validation
  3. The synthesis of indolo[2,3-b]quinoline derivatives with a guanidine group: highly selective cytotoxic agents

The synthesis of indolo[2,3-b]quinoline derivatives with a guanidine group: highly selective cytotoxic agents

  • Eur J Med Chem. 2015 Nov 13:105:208-19. doi: 10.1016/j.ejmech.2015.10.022.
Katarzyna Sidoryk 1,  Marta Świtalska 2,  Anna Jaromin 3,  Piotr Cmoch 4,  Iwona Bujak 5,  Monika Kaczmarska 5,  Joanna Wietrzyk 6,  Eddie G Dominguez 7,  Robert Żarnowski 7,  David R Andes 7,  Krzysztof Bańkowski 5,  Marcin Cybulski 5,  Łukasz Kaczmarek 5
Affiliations

Affiliations

  • 1 Pharmaceutical Research Institute, 8 Rydygiera St., 01-793 Warsaw, Poland. Electronic address: k.sidoryk@ifarm.eu.
  • 2 Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St., 53-114 Wroclaw, Poland.
  • 3 Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, 14A Joliot-Curie St., 50-383 Wroclaw, Poland.
  • 4 Pharmaceutical Research Institute, 8 Rydygiera St., 01-793 Warsaw, Poland; Institute of Organic Chemistry, Polish Academy of Sciences, 44/52 Kasprzaka St., 01-224 Warsaw, Poland.
  • 5 Pharmaceutical Research Institute, 8 Rydygiera St., 01-793 Warsaw, Poland.
  • 6 Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St., 53-114 Wroclaw, Poland; Institute of Chemistry Environmental Protection and Biotechnology, Jan Długosz University, 13/15 Armii Krajowej Ave., 42-200 Częstochowa, Poland.
  • 7 Department of Medicine, Section of Infectious Diseases, 4125 Microbial Sciences Building, 1550 Linden Dr., University of Wisconsin-Madison, Madison, WI 53706, USA.
PMID: 26496013 DOI: 10.1016/j.ejmech.2015.10.022
Abstract

The synthesis of indolo[2,3-b]quinoline derivatives containing guanidine, amino acid or guanylamino acid substituents as well as their in vitro evaluation for the cytotoxic and Antifungal activity are reported. The influence of the guanidine group on the selective cytotoxic and hemolytic properties of indolo[2,3-b]quinoline was investigated. Most of the compounds displayed a high cytotoxic activity in vitro and two of the most promising compounds (3 and 12) exhibited a high selectivity between normal and Cancer cell-lines. The cytotoxic activity of compound 3 was about 600-fold lower against normal fibroblasts than against A549 and MCF-7 Cancer cell lines. Novel entities acted as the DNA-intercalators when tested using a DNA-methyl green assay but demonstrated zero or low hemolytic activity in comparison to their unsubstituted analogs. The mechanism of action was studied for guanidine derivatives 3 and 12 and both compounds were found to be very effective inducers of Apoptosis.

Keywords

Antifungal activity; Antiproliferative activity; Apoptosis; Biofilm; Guanidine group; Hemolytic activity; Mechanism of action; Neocryptolepine.

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