Design, synthesis and cytotoxic activity of water-soluble quinones with dibromo- p-benzoquinone cores and amino oligo(ethylene glycol) side chains against MCF-7 breast cancer cells

Leon F Scherz; Engy A Abdel-Rahman; Sameh S Ali; A Dieter Schlüter; Mona A Abdel-Rahman

doi:10.1039/c6md00728g

Design, synthesis and cytotoxic activity of water-soluble quinones with dibromo- p-benzoquinone cores and amino oligo(ethylene glycol) side chains against MCF-7 breast cancer cells

Medchemcomm. 2017 Feb 16;8(3):662-672. doi: 10.1039/c6md00728g. eCollection 2017 Mar 1.

Authors

Leon F Scherz¹, Engy A Abdel-Rahman^{2

3}, Sameh S Ali³, A Dieter Schlüter¹, Mona A Abdel-Rahman⁴

Affiliations

¹ Institute of Polymers , Department of Materials , ETH Zürich , 8093 Zürich , Switzerland.
² Pharmacology Department , Faculty of Medicine , Assiut University , 71515 Assiut , Egypt.
³ Center for Aging and Associated Diseases , Helmy Institute of Medical Science , Zewail City of Science and Technology , 12588 Giza , Egypt.
⁴ Chemistry Department , Polymer Lab. 109 , Faculty of Science , Assiut University , 71516 Assiut , Egypt . Email: mona.ali1@aun.edu.eg.

Abstract

A series of novel quinones was synthesized by reacting tetrabromo-p-benzoquinone with amino oligo(ethylene glycol) dendrons of generation numbers g = 0-2. According to the performed shake-flask experiments, their aqueous solubility (S = 18 mg l^-1-1.6 g ml^-1) and partition coefficients (log P_oct/wat = 2.53-0.21) can be tuned in a wide range as a function of g. In vitro cytotoxicity assays of tetrabromo-p-benzoquinone and its derivatives against MCF-7 human breast cancer cells showed a concentration- and generation-specific biological activity with IC₅₀-values as low as 0.8 μM. Further investigations revealed a considerable selectivity against cancer cells, as indicated by a weak cytotoxicity against human skin fibroblast cells (>80% survival) within the studied range of concentrations. The results demonstrate that these novel amino oligo(ethylene glycol) dendrons depict versatile tools to ameliorate physical and pharmacological characteristics of extremely hydrophobic molecules and make them susceptible to biological applications.