Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents

  • Bioorg Med Chem Lett. 2016 Feb 15;26(4):1145-50. doi: 10.1016/j.bmcl.2016.01.048.
Sonia Stoica  1 ,  George E Magoulas  2 ,  Antonia I Antoniou  2 ,  Sherif Suleiman  1 ,  Analisse Cassar  1 ,  Lucienne Gatt  1 ,  Dionissios Papaioannou  2 ,  Constantinos M Athanassopoulos  3 ,  Pierre Schembri-Wismayer  4
Affiliations
  • 1. Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta.
  • 2. Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.
  • 3. Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece. Electronic address: [email protected].
  • 4. Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta. Electronic address: [email protected].
PMID: 26832215 DOI: 10.1016/j.bmcl.2016.01.048
Abstract

Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 Acute Myeloid Leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 μM without being toxic on proliferating human peripheral blood mononuclear cells.

Keywords
Conjugates; Differentiation; HL-60; Minoxidil; Polyamines.