Novel 4,4'-diether-2,2'-bipyridine cisplatin analogues are more effective than cisplatin at inducing apoptosis in cancer cell lines.

The synthesis and characterization of dichloro(4,4'-bis[methoxy]-2,2'-bipyridine)platinum (1) and dichloro(4,4'-bis[3-methoxy-n-propyl]-2,2'-bipyridine)platinum (2) are described. As analogues to CDDP, these 4,4'-disubstituted 2,2'-bipyridine complexes exhibit decreased EC(50) values of 10-100 times in cancer cell lines of the lung, prostate, and melanoma with several combinations of complex and cell line less than 10 microM. Flow cytometry data indicate 'blocks' of MDA-MD-435 cycle by 1 (G2/M) and 2 (S). Observed cell survival trends in the presence of 1, 2 under ionizing radiation mimic those of CDDP. Preliminary structure activity relationships are discussed for the 4,4'-substitutions made on the bipyridine ring. Copyright (c) 2009 Elsevier Ltd. All rights reserved.