Caron Giulia, Ermondi Giuseppe, Gariboldi Marzia B, Monti Elena, Gabano Elisabetta, Ravera Mauro, Osella Domenico
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, 10125 Torino (Italy).
ChemMedChem. 2009 Oct;4(10):1677-85. doi: 10.1002/cmdc.200900224.
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.
设计并合成了一组六种顺二氨基丙二酸铂（II）衍生物，并通过实验评估了它们的物理化学性质和体外生物活性，并进行了计算机模拟研究。在三种不同的人类肿瘤细胞系，即A2780卵巢癌、A549肺癌和MCF-7乳腺癌细胞系上，所有这些配合物的IC(50)值均高于顺铂及其丙二酸类似物（≥20 microM）。计算机模拟研究表明，极性表面积（PSA）是解释该系列新化合物生物活性不佳的最佳描述符，而这反过来可能是由于细胞摄取不良所致。这一发现符合一般规律，即在抗增殖金属药物的实际情况下，PSA在表征药物转运性质方面起着主要作用。
