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

Waldemar Goldeman; Anna Nasulewicz-Goldeman

doi:10.1016/j.bmcl.2014.05.071

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. Epub 2014 Jun 2.

Authors

Waldemar Goldeman¹, Anna Nasulewicz-Goldeman²

Affiliations

¹ Wrocław University of Technology, Department of Organic Chemistry, Wybrzeże Wyspiańskiego 27, Wrocław 50-370, Poland. Electronic address: waldemar.goldeman@pwr.wroc.pl.
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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

1-Naphthylamine / analogs & derivatives*
1-Naphthylamine / chemical synthesis
1-Naphthylamine / chemistry
1-Naphthylamine / pharmacology
Aniline Compounds / chemical synthesis
Aniline Compounds / chemistry
Aniline Compounds / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Diphosphonates / chemical synthesis
Diphosphonates / chemistry
Diphosphonates / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HL-60 Cells
Humans
MCF-7 Cells
Macrophages / drug effects*
Molecular Structure
Phenylenediamines / chemical synthesis
Phenylenediamines / chemistry
Phenylenediamines / pharmacology*
Structure-Activity Relationship

Substances

Aniline Compounds
Antineoplastic Agents
Diphosphonates
Phenylenediamines
benzene-1,4-bis(aminomethylidene(bisphosphonic)) acid
naphthalene-1,5-bis(aminomethylidene(bisphosphonic)) acid
sulfonyldiphenyl-4,4'-bis(aminomethylidene(bisphosphonic)) acid
1-Naphthylamine