A new antioxidative vitamin B6 analogue modulates pathophysiological cell proliferation and damage.
The new large scale synthesis of the yellow colored vitamin B6 analogue 5'-O-phosphono-pyridoxylidenerhodanine (2) (B6PR) leads to oligohydrates of its monosodium salt (4). The light-red hemiheptadecahydrate (8 1/2 hydrate) (4a) was crystallized and its three-dimensional structure determined by X-ray crystallography. Special nucleotide and protein interaction properties together with scavenging antioxidative function are combined in this simple water-soluble vitamin B6 analogues B6PR. High (mM) concentrations were untoxic to 'healthy' not affected cells and primary tissues. Complexation of ions (e.g. Ca2+, Fe2+, and Zn2+), modulation of nitric oxide synthases (NOS I-III), nitric oxide (NO) metabolism, and reactive oxygen species (ROS) was found. Special cytoprotecting, immunomodulating, stimulating and inhibiting activities were observed in vitro, not in comparison with some natural and synthetic pyridoxines. Low B6PR suppressed proliferation, high induced selective cell death of some cancer cell lines. Low B6PR protected HIV-1-infected CD4+ HUT 78 cells against HIV-1-mediated destruction (complete inhibition of HIV-1-induced syncytia formation and cell death) and reduced p24 level. Autoreactive S100beta-specific T cells of Lewis rat, a model of multiple sclerosis, could be influenced. Oxidative damage and age, acquired and inherited disease related pathophysiological disorders can be treated by this new cytopathology-selective versatile acting B6PR.
Kesel
A J
AJ
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Sonnenbichler
I
I
Polborn
K
K
Gürtler
L
L
Klinkert
W E
WE
Modolell
M
M
Nüssler
A K
AK
Oberthür
W
W
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D009573:Nitrites / Q000378:metabolism; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000737:chemistry*; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009573:Nitrites; D011736:Pyridoxine