Biological activity of a series of cisplatin-based aliphatic bis(carboxylato) Pt(IV) prodrugs: How long the organic chain should be?

Biological activity of a series of cisplatin-based aliphatic bis(carboxylato) Pt(IV) prodrugs: How long the organic chain should be? J Inorg Biochem. 2014 Aug 7;140C:219-227 Authors: Zanellato I, Bonarrigo I, Colangelo D, Gabano E, Ravera M, Alessio M, Osella D Abstract The biological properties of a series of cisplatin-based Pt(IV) prodrug candidates, namely trans,cis,cis-[Pt(carboxylato)2Cl2(NH3)2], where carboxylato=CH3(CH2)nCOO(-) [(1), n=0; (2), n=2; (3), n=4; (4), n=6] having a large interval of lipophilicity are discussed. The stability of the complexes was tested in different pH conditions (i.e. from 1.0 to 9.0) to simulate the hypothetical conditions for an oral route of administration, showing a high stability (>90%). The transformation into their active Pt(II) metabolites was demonstrated in the presence of ascorbic acid, with a pseudo-first order kinetics, the half-time of which smoothly decreases as the chain length of carboxylic acid increases. Their antiproliferative activity has been evaluated in vitro on a large panel of human cancer cell lines. As expected, the potency increases with the chain length: 3 and 4 resulted by far more active than cisplatin on all cell lines of about one or two orders of magnitude, respectively. Both complexes retained their activity also on cisplatin-resistant cell line, and exhibited a progressive increase of the selectivity compared with non-tumor cells. These results were confirmed...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research