We examined the cytotoxicity and cellular uptake in L1210 murine
leukemia cells, as well as the coordinative reaction with the
guanine derivative
9-ethylguanine (9EtG), of a series of μ-hydroxo-μ-tetrazolato dinuclear
platinum(II) complexes (tetrazolato-bridged complexes), [{cis-Pt(NH3)2}2(μ-
OH)(μ-tetrazolato-N1,N2)](2+) (5-H-X) and [{cis-Pt(NH3)2}2(μ-
OH)(μ-5-R-tetrazolato-N2,N3)](n+), where R = H (5-H-Y), CH3 (1), C6H5 (2), CH2COOCH2CH3 (3), or CH2COO(-) (4), and n = 2 (5-H-Y, 1-3) or 1 (4). Most tetrazolato-bridged complexes overcame cross-resistance to
cisplatin and were more efficiently taken up into
cisplatin-resistant cells (L1210R) than into parental
cisplatin-sensitive cells (L1210), whereas
cisplatin uptake into L1210R was decreased compared with that into L1210. The cellular uptake was most likely controlled by the total charge of the complexes. There was no correlation between the cytotoxicity and the kinetics of the coordinative reactions of 1-4 with 9EtG, but the isomerization involved in the reactions could contribute to determining the higher order structures of the compacted
DNA. The cytotoxicity of tetrazolato-bridged complexes appears to correlate with the efficiency of cellular uptake and
DNA compaction.