New Analogs of Polyamine Toxins from Spiders and Wasps: Liquid Phase Fragment Synthesis and Evaluation of Antiproliferative Activity
Christos Vassileiou,
Stefania Kalantzi,
Eleanna Vachlioti,
Constantinos M. Athanassopoulos,
Christos Koutsakis,
Zoi Piperigkou,
Nikos Karamanos,
Theodora Stivarou,
Peggy Lymberi,
Konstantinos Avgoustakis,
Dionissios Papaioannou
Affiliations
Christos Vassileiou
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Stefania Kalantzi
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Eleanna Vachlioti
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Constantinos M. Athanassopoulos
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Christos Koutsakis
Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Zoi Piperigkou
Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Nikos Karamanos
Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Theodora Stivarou
Immunology Laboratory, Department of Immunology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, Ampelokipi, 115 21 Athens, Greece
Peggy Lymberi
Immunology Laboratory, Department of Immunology, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, Ampelokipi, 115 21 Athens, Greece
Konstantinos Avgoustakis
Department of Pharmacy, University of Patras, 265 04 Patras, Greece
Dionissios Papaioannou
Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, 265 04 Patras, Greece
Polyamine toxins (PATs) are conjugates of polyamines (PAs) with lipophilic carboxylic acids, which have been recently shown to present antiproliferative activity. Ten analogs of the spider PATs Agel 416, HO-416b, and JSTX-3 and the wasp PAT PhTX-433 were synthesized with changes in the lipophilic head group and/or the PA chain, and their antiproliferative activity was evaluated on MCF-7 and MDA-MB-231 breast cancer cells, using Agel 416 and HO-416b as reference compounds. All five analogs of PhTX-433 were of very low activity on both cell lines, whereas the two analogs of JSTX-3 were highly active only on the MCF-7 cell line with IC50 values of 2.63–2.81 μΜ. Of the remaining three Agel 416 or HO-416b analogs, only the one with the spermidine chain was highly active on both cells with IC50 values of 3.15–12.6 μM. The two most potent compounds in this series, Agel 416 and HO-416b, with IC50 values of 0.09–3.98 μΜ for both cell lines, were found to have a very weak cytotoxic effect on the MCF-12A normal breast cells. The present study points out that the structure of both the head group and the PA chain determine the strength of the antiproliferative activity of PATs and their selectivity towards different cells.
