Synthesis of Minoxidil Conjugates and Their Evaluation as HL-60 Differentiation Agents

In the 2016 study by Stoica et al., researchers synthesized minoxidil (MNX) conjugates to assess their ability to induce differentiation in HL-60 acute myeloid leukemia cells. The conjugates were created by combining MNX with natural polyamines and various amines. The study revealed that MNX alone did not induce differentiation, but specific conjugates, particularly the MNX-spermine (SPM) conjugate (11) and conjugates 7 and 8 with 4,4'-methylenedianiline (MDA) and 2,7-diaminofluorene (DAF), did show differentiation effects at 10 µM concentration without being toxic to proliferating human peripheral blood mononuclear cells. These findings suggest that MNX conjugation with certain amines can enhance its biological activity and could provide a targeted approach to leukemia treatment with reduced cytotoxicity. Further research is needed to expand the library of MNX-amine and -polyamine conjugates and to understand the mechanisms behind the differentiation induction.