The relevance of polar surface area (PSA) in rationalizing biological properties of several cis-diamminemalonatoplatinum(II) derivatives.
A panel of six cis-diamminemalonatoplatinum(II) derivatives were designed and synthesized, and their physicochemical properties and in vitro biological activity were experimentally evaluated and studied in silico. All the complexes showed higher IC(50) values (> or =20 microM) than those observed for cisplatin and its malonato analogue on three different human tumor cell lines, namely A2780 ovarian carcinoma, A549 lung carcinoma, and MCF-7 breast carcinoma. In silico studies revealed that polar surface area (PSA) is the best descriptor to explain the poor biological activity observed for this series of new compounds, which in turn is likely due to poor cellular uptake. This finding is in line with general rules that assign a major role to PSA in characterizing the transport properties of drugs, in the actual case of antiproliferative metallopharmaceuticals.
Caron
Giulia
G
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, 10125 Torino (Italy).
Ermondi
Giuseppe
G
Gariboldi
Marzia B
MB
Monti
Elena
E
Gabano
Elisabetta
E
Ravera
Mauro
M
Osella
Domenico
D
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001681:Biological Assay; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50
D000970:Antineoplastic Agents; D002945:Cisplatin