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The Relevance of Polar Surface Area (PSA) in Rationalizing Biological Properties of Several cis ‐Diamminemalonatoplatinum(II) Derivatives
Author(s) -
Caron Giulia,
Ermondi Giuseppe,
Gariboldi Marzia B.,
Monti Elena,
Gabano Elisabetta,
Ravera Mauro,
Osella Domenico
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900224
Subject(s) - in silico , biological activity , polar surface area , in vitro , human lung , cisplatin , chemistry , carcinoma , carcinoma cell , ovarian carcinoma , human breast , stereochemistry , breast carcinoma , cell culture , cancer research , biochemistry , computational biology , biology , cancer , molecule , organic chemistry , genetics , ovarian cancer , breast cancer , chemotherapy , gene
Abstract 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 (≥20 μ M ) 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.