TY - JOUR
T1 - Platinum(II) and technetium(I) complexes anchored to ethynylestradiol
T2 - A way to drug targeting and delivery
AU - Cassino, Claudio
AU - Gabano, Elisabetta
AU - Ravera, Mauro
AU - Cravotto, Giancarlo
AU - Palmisano, Giovanni
AU - Vessières, Anne
AU - Jaouen, G. Érard
AU - Mundwiler, Stefan
AU - Alberto, Roger
AU - Osella, Domenico
N1 - Funding Information:
This work was financially supported by MIUR (Roma) within COFIN2001 project and by C.I.R.C.M.S.B. (Bari). We are indebted to Johnson Matthey (Reading, UK) for a generous loan of K 2 [PtCl 4 ]. This research was carried out in the frame of the European Cooperation COST D20 action (metal compounds in the treatment of cancer and viral diseases) and COST B16 action (multidrug resistance reversal).
PY - 2004/5/10
Y1 - 2004/5/10
N2 - 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.
AB - 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.
KW - Platinum
KW - Receptor
KW - Steroids
KW - Technetium
UR - http://www.scopus.com/inward/record.url?scp=11144356615&partnerID=8YFLogxK
U2 - 10.1016/j.ica.2003.12.016
DO - 10.1016/j.ica.2003.12.016
M3 - Article
SN - 0020-1693
VL - 357
SP - 2157
EP - 2166
JO - Inorganica Chimica Acta
JF - Inorganica Chimica Acta
IS - 7
ER -