title: Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents.
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.
authors.affiliation: Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta.
authors.forename: Sonia
authors.initials: S
authors.lastname: Stoica
authors.affiliation: Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.
authors.forename: George E
authors.initials: GE
authors.lastname: Magoulas
authors.affiliation: Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.
authors.forename: Antonia I
authors.initials: AI
authors.lastname: Antoniou
authors.affiliation: Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta.
authors.forename: Sherif
authors.initials: S
authors.lastname: Suleiman
authors.affiliation: Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta.
authors.forename: Analisse
authors.initials: A
authors.lastname: Cassar
authors.affiliation: Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Gatt
authors.affiliation: Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece.
authors.forename: Dionissios
authors.initials: D
authors.lastname: Papaioannou
authors.affiliation: Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, GR-26504 Patras, Greece. Electronic address: kath@chemistry.upatras.gr.
authors.forename: Constantinos M
authors.initials: CM
authors.lastname: Athanassopoulos
authors.affiliation: Anatomy Department, Faculty of Medicine and Surgery, University of Malta, Malta. Electronic address: pierre.schembri-wismayer@um.edu.mt.
authors.forename: Pierre
authors.initials: P
authors.lastname: Schembri-Wismayer
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005449:Fluorenes / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D008914:Minoxidil / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry; D013096:Spermine / Q000737:chemistry; D001559:Benzhydryl Compounds
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D005449:Fluorenes; D007093:Imidazoles; D008914:Minoxidil; D011073:Polyamines; D013096:Spermine; C006900:N,N-carbonyldiimidazole; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds; C012978:2,7-fluorenediamine
keywords: Conjugates; Differentiation; HL-60; Minoxidil; Polyamines