Anthracene-Derived Bis-Aminophosphonates: Crystal Structure, In Vitro Antitumor Activity, and Genotoxicity In Vivo

Abstract

The X-ray crystal structures of the anthracene-derived bis-aminophosphonates 4.4′-bis[N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]diaminodiphenylmethane (1) and 1,3-bis

[N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]diaminobenzene (3) are reported. The X-ray analyses demonstrated that both compounds crystallize in a centrosymmetric manner containing a meso-form (1) and a pair of enantiomers (3).

The cytotoxic potential, genotoxicity, and antiproliferative activity of bis-aminophosphonates 1 and bis[N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]benzidine (2), as well as their subcellular distribution in a tumor cell culture system, are also discussed. Compounds 1 and 2 showed optimal antiproliferative activity to human tumor cells from colon carcinoma line HT-29. In vitro and in vivo safety testing revealed that the compounds exert lower toxicity to normal cells as compared with well-known anticancer and cytotoxic agents.

Supplemental materials are available for this article. Go to the publisher's online edition ofPhosphorus, Sulfur, and Silicon and the Related Elementsto view the free supplemental file.

GRAPHICAL ABSTRACT

Keywords:

• Aminophosphonic acids
• single crystal
• antitumor activity
• in vitro cytotoxicity
• genotoxicity

Acknowledgments

Thanks are due to Bulgarian National Science Fund of Ministry of Education and Science for the financial support: contract DTK-02/34 (2009).