Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids

  • Bioorg Med Chem Lett. 2014 Aug 1;24(15):3475-9. doi: 10.1016/j.bmcl.2014.05.071.
Waldemar Goldeman  1 ,  Anna Nasulewicz-Goldeman  2
Affiliations
  • 1. Wrocław University of Technology, Department of Organic Chemistry, Wybrzeże Wyspiańskiego 27, Wrocław 50-370, Poland. Electronic address: [email protected].
  • 2. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy, Rudolfa Weigla 12, Wrocław 53-114, Poland.
PMID: 24928399 DOI: 10.1016/j.bmcl.2014.05.071
Abstract

A series of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids was synthesized in the reaction of triethylphosphite with isonitriles followed by hydrolysis or dealkylation. The in vitro anti-proliferative effect of all synthesized tetraphosphonic acids against MCF-7 breast Cancer cells, J774E macrophages and HL-60 promyelocytic leukemia cells was determined. Three aromatic derivatives (5a, 5f and 5j) showed a similar or higher anti-proliferative activity than zoledronic acid.

Keywords
Anti-proliferative activity; Bisphosphonate; Bisphosphonic acid; Isocyanide; Isonitrile; Osteoclasts; Tetraphosphonate; Tumor cells.