1981 Volume 29 Issue 4 Pages 929-939
Platinum (II) complexes of the type [PtX (1, 3-diamine)] (X=Cl2, SO4, (NO3)2, oxalato, D-glucuronato, and D-gluconato ; 1, 3-diamine=2-(aminomethyl) cyclohexylamine, 2, 4-pentanediamine, 1, 3-butanediamine, and 1, 3-diphenyl-1, 3-propanediamine isomers) were prepared, and their antitumor activity against leukemia L1210 was tested according to the protocol recommended by the National Cancer Institute for the evaluation of Pt analogs. A large number of long-term survivors was observed with certain analogs, though the therapeutic indices were not large. Among the platinum (II) complexes tested so far, trans-l- and cis-l-2-(aminomethyl) cyclohexylamine platinum (II) complexes showed marked antitumor activity, while 1, 3-diphenyl-1, 3-propane diamine platinum (II) complexes were almost inactive because of their low solubility in water. The structures of the complexes are discussed on the basis of the circular dichroism (CD) and 13C-nuclear magnetic resonance (NMR) spectral data. The structure of the cis-l-2-(aminomethyl) cyclohexylamine complex was much more flexible than that of the trans-l-2-(aminomethyl) cyclohexylamine complex, and the cyclohexane ring and the chelate ring of the latter lie in a common plane. The coplanarity of trans-2-(aminomethyl) cyclohexylamine and the flexibility of cis-2-(aminomethyl) cyclohexylamine may allow them to approach the target DNA relatively easily.
