Platinum(II) and technetium(I) complexes anchored to ethynylestradiol: A way to drug targeting and delivery

Claudio Cassino, Elisabetta Gabano, Mauro Ravera, Giancarlo Cravotto, Giovanni Palmisano, Anne Vessières, G. Érard Jaouen, Stefan Mundwiler, Roger Alberto, Domenico Osella

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Starting from ethynylestradiol (1), or, more precisely, from its 3,17β-bis-(triethylsilyloxy) derivative 2, two new ligands containing the ethylenediamino motif were synthesised by a Mannich aminomethylation, namely N-methyl-N-(prop-2-ynyl-3-(17α-estradiolyl))-N,N -dimethylethylenediamine (3) and N-(prop-2-ynyl-3-(17α- estradiolyl))-N-methylpiperazine (4). The corresponding platinum(II)-malonato complexes (7 and 8) were prepared through the PtI 2 intermediates (namely 5 and 6) by Dhara's method. The structures of the two platinum complexes were energy-minimised by molecular mechanics employing the Amber force field. Both ligands were joined to the [ 99mTc(CO)3Cl] moiety, 99mTc being the chief γ-emitter employed in nuclear medicine. Unfortunately, piperazine ligand 4 afforded complexes that were unstable under physiological conditions. The RBA values for both ligands and complexes derived from 3, measured for the two forms of estrogen receptor, were less than 1%. Such a poor degree of ligand recognition may be due to the partial protonation of the amino groups at physiological pH, making the carrier quite hydrophilic, therefore unsuitable for entering the hydrophobic pocket of estrogen receptors.

Lingua originaleInglese
pagine (da-a)2157-2166
Numero di pagine10
RivistaInorganica Chimica Acta
Volume357
Numero di pubblicazione7
DOI
Stato di pubblicazionePubblicato - 10 mag 2004

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