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

Sonia Stoica; George E Magoulas; Antonia I Antoniou; Sherif Suleiman; Analisse Cassar; Lucienne Gatt; Dionissios Papaioannou; Constantinos M Athanassopoulos; Pierre Schembri-Wismayer

doi:10.1016/j.bmcl.2016.01.048

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. Epub 2016 Jan 19.

Authors

Sonia Stoica¹, George E Magoulas², Antonia I Antoniou², Sherif Suleiman¹, Analisse Cassar¹, Lucienne Gatt¹, Dionissios Papaioannou², Constantinos M Athanassopoulos³, Pierre Schembri-Wismayer⁴

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: kath@chemistry.upatras.gr.
⁴ Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta. Electronic address: pierre.schembri-wismayer@um.edu.mt.

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.

MeSH terms

Aniline Compounds / chemistry
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Fluorenes / chemistry
HL-60 Cells
Humans
Imidazoles / chemistry
Minoxidil / chemistry*
Polyamines / chemistry
Spermine / chemistry

Substances

Aniline Compounds
Antineoplastic Agents
Fluorenes
Imidazoles
Polyamines
Spermine
Minoxidil
N,N-carbonyldiimidazole
4,4'-diaminodiphenylmethane
2,7-fluorenediamine