Synthesis and biological activity of new melatonin dimeric derivatives.
A new series of melatonin (MLT) dimers were obtained by linking together two melatonin units with a linear alkyl chain through the MLT acetamido group or through a C-2 carboxyalkyl function. The binding properties of these ligands were evaluated in in vivo experiments on cloned human MT(1) and MT(2) receptors expressed in NIH3T3 rat fibroblast cells. The class of 2-carboxyalkyl dimers was the most interesting one with compounds having good MT(1)/MT(2) nanomolar affinity. The data obtained suggest that the spacer length is crucial for optimal interaction at both receptor subtypes as well as to determine functional activity of the resulting dimers.
Di Giacomo
Barbara
B
Istituto di Chimica Farmaceutica, Università degli Studi di Urbino Carlo Bo, 61029 Urbino, Italy. barbara@uniurb.it
Bedini
Annalida
A
Spadoni
Gilberto
G
Tarzia
Giorgio
G
Fraschini
Franco
F
Pannacci
Marilou
M
Lucini
Valeria
V
D016475:3T3 Cells; D000818:Animals; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D051381:Rats; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects
D007202:Indicators and Reagents; D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008550:Melatonin