cis-Pt I-2(NH3)(2): a reappraisal

0457640 - BFÚ 2016 RIV GB eng J - Journal Article
Marzo, T. - Pillozzi, S. - Hrabina, O. - Kašpárková, Jana - Brabec, Viktor - Arcangeli, A. - Bartoli, G. - Severi, M. - Lunghi, A. - Totti, F. - Gabbiani, C. - Quiroga, Adoración G. - Messori, L.
cis-Pt I-2(NH3)(2): a reappraisal.
Dalton Transactions. Roč. 44, č. 33 (2015), s. 14896-14905. ISSN 1477-9226. E-ISSN 1477-9234
R&D Projects: GA ČR(CZ) GA14-21053S
Institutional support: RVO:68081707
Keywords : PLATINUM ANTICANCER DRUGS * CRYSTAL-STRUCTURE * COMPLEXES
Subject RIV: BO - Biophysics
Impact factor: 4.177, year: 2015

The investigation of cis-PtI2(NH3)(2), the diiodido analogue of cisplatin (cisPtI(2) hereafter), has been unjustly overlooked so far mainly because of old claims of pharmacological inactivity. Some recent -but still fragmentary - findings prompted us to reconsider more systematically the chemical and biological profile of cisPtI(2) in comparison with cisplatin. Its solution behaviour, interactions with DNA and cytotoxic properties versus selected cancer cell lines were thus extensively analysed through a variety of biophysical and computational methods. Notably, we found that cisPtI(2) is highly cytotoxic in vitro toward a few solid tumour cell lines and that its DNA platination pattern closely reproduces that of cisplatin; cisPtI(2) is also shown to completely overcome resistance to cisplatin in a platinum resistant cancer cell line. The differences in the biological actions of these two Pt complexes are most likely related to slight but meaningful differences in their solution behaviour and reactivity. Overall, a very encouraging and unexpected pharmacological profile emerges for cisPtI(2) with relevant implications both in terms of mechanistic knowledge and of prospective clinical application.
Permanent Link: http://hdl.handle.net/11104/0258041