TY - JOUR
T1 - Antiproliferative activity of PtII complexes with carboxylated phosphanes in chelated or ring-opened forms
AU - Ravera, Mauro
AU - Gabano, Elisabetta
AU - Sardi, Manuele
AU - Monti, Elena
AU - Gariboldi, Marzia B.
AU - Osella, Domenico
PY - 2012/7
Y1 - 2012/7
N2 - The biological activity of four cisplatin-like Pt-phosphane complexes, namely, cis-[PtCl2(L)2], L = PPh3, P(Ph) 2(p-C6H4-COOH), P(Ph)2(-CH 2CH2-COOH) and its succinimidyl ester derivative, has been tested on monolayer cultures of three tumour cell lines (namely, A2780 human ovarian carcinoma and its cisplatin-resistant form A2780Cp8, and human colon adenocarcinoma HCT116). These complexes can undergo intramolecular rearrangements by virtue of their functionalized phosphanes, thereby existing as fully opened (O) or fully closed (C) forms. Our results show that only the opened forms exhibit moderate activity, which, although inferior to the activity exhibited by the archetype metallo-drug cisplatin, is substantially retained in the A2780Cp8 cell line, yielding very low resistance factors. The trend is also maintained on the less cisplatin-sensitive HCT116 line. When the complexes assume the bis-chelated (C) form, the antiproliferative activity is deeply reduced. Two Pt-amine congeners, containing β-alanine and 3-methoxypropylamine, with C and O structures, respectively, were synthesized and their antiproliferative propensity was evaluated for comparison purposes, and a similar scenario was observed. The biological activity of four cisplatin-like Pt-phosphane complexes has been tested. Some of the complexes can undergo intramolecular rearrangement by virtue of the functionalized phosphanes (fully opened/fully closed forms). The results show that only the opened forms exhibit moderate activity, which is substantially retained in the cisplatin-resistant cell lines.
AB - The biological activity of four cisplatin-like Pt-phosphane complexes, namely, cis-[PtCl2(L)2], L = PPh3, P(Ph) 2(p-C6H4-COOH), P(Ph)2(-CH 2CH2-COOH) and its succinimidyl ester derivative, has been tested on monolayer cultures of three tumour cell lines (namely, A2780 human ovarian carcinoma and its cisplatin-resistant form A2780Cp8, and human colon adenocarcinoma HCT116). These complexes can undergo intramolecular rearrangements by virtue of their functionalized phosphanes, thereby existing as fully opened (O) or fully closed (C) forms. Our results show that only the opened forms exhibit moderate activity, which, although inferior to the activity exhibited by the archetype metallo-drug cisplatin, is substantially retained in the A2780Cp8 cell line, yielding very low resistance factors. The trend is also maintained on the less cisplatin-sensitive HCT116 line. When the complexes assume the bis-chelated (C) form, the antiproliferative activity is deeply reduced. Two Pt-amine congeners, containing β-alanine and 3-methoxypropylamine, with C and O structures, respectively, were synthesized and their antiproliferative propensity was evaluated for comparison purposes, and a similar scenario was observed. The biological activity of four cisplatin-like Pt-phosphane complexes has been tested. Some of the complexes can undergo intramolecular rearrangement by virtue of the functionalized phosphanes (fully opened/fully closed forms). The results show that only the opened forms exhibit moderate activity, which is substantially retained in the cisplatin-resistant cell lines.
KW - Antiproliferation
KW - Biological activity
KW - Intramolecular rearrangement
KW - Phosphane ligands
KW - Platinum
UR - http://www.scopus.com/inward/record.url?scp=84863824558&partnerID=8YFLogxK
U2 - 10.1002/ejic.201200282
DO - 10.1002/ejic.201200282
M3 - Article
SN - 1434-1948
SP - 3441
EP - 3448
JO - European Journal of Inorganic Chemistry
JF - European Journal of Inorganic Chemistry
IS - 21
ER -