Synthesis, crystal structure, and biological activity of a Pt-dipyridamole salt.

In the present paper we present data on the synthesis, crystal structure and biological activity of bis(dipyridamole) tetrachloroplatinate(II).dipyridamole.dihydrate, [dpmH]2 PtCl4.dpm.2H2O. The crystals are Triclinic P1 with a = 11.490(2) A, b = 13.630(2) A, c = 15.81(1) A, a = 100.97(2) degrees, beta = 100.89(3) degrees, gamma = 112.35(1) degrees, Z = 1, M = 1885.9, Dx = 1.46 g/cm3, MoK alpha (lambda = 0.71069 A), mu = 0.0184 mm-1, R = 4.4%, Rw = 5.0%, 3231 (1 > 2 sigma (I)). The structure is stabilized by a hydrogen-bonding network. It was observed that although dpm alone is not able to alter the electrophoretic mobility of pUC8 DNA forms, the synthesized Pt-dpm compound substantially modifies the DNA conformation since it significantly alters the electrophoretic mobility of nicked and closed circular forms of pUC8 DNA. However, the alteration in mobility of pUC8 DNA induced by this compound upon binding is lower than that induced by cis-DDP. The analysis of the antiproliferative activity of the Pt-dpm salt against MDA-MB 468 (breast carcinoma) and HL-60 (leukemia) human cancer cells showed that this compound has ID50 values of 0.87 microM and 0.65 microM, respectively. Interestingly, it was found out that although the dpm molecule does not present any significant antiproliferative activity, the ID50 values of Pt-dpm are about 3-fold and 7-fold lower than those of cis-DDP and K2PtCl4, respectively. Altogether the biological data suggest that in Pt-dpm a synergic effect between cation and anion is produced.