SYNTHESIS AND ANTITUMOR-ACTIVITY OF THE METFORMIN PLATINUM(IV) COMPLEX - CRYSTAL-STRUCTURE OF THE TETRACHLORO(METFORMIN)PLATINUM(IV) DIMETHYLSULFOXIDE SOLVATE

The synthesis of (metaformin) tetrachloroplatinum (IV) was investigate d (metaformin is N, N-dimethylbiguanide). It crystallizes with one dim ethylsulfoxide molecule rls solvate in the monoclinic system, space gr oup P2(1)/n (No. 14) with Z=4. The cell dimensions are: a = 13.136(7), b = 9.424(2) c = 14.009(8) Angstrom, beta = 111.96(4)degrees, V = 160 8.4(2) Angstrom(3). Of the 4269 independent nonzero reflections collec ted, 1979 with I > 3 sigma(I) were considered and used in the calculat ions. The structure was refined to R = 0. 043 and wR = 0.045. The plat inum coordination is octahedral, built up from four chloride anions an d one bidentate chelating ligand via the two imine nitrogen atoms cis position. The distances and angles are typical of six-membered rings t hat have similar donor atoms. The complex was evaluated in vitro and i n vivo on murine P388 leukemia. It was found to be as potent as cis-di chlorodiammine platinum (II), CDDP, in inhibiting the proliferation of the sensitive P388 cells. However the resistant P388/CDDP cells were threefold more sensitive to the compound than to CDDP. The two compoun ds induced a similar perturbation in the G2 + M phases of the cell-cyc le. The complex was less active than CDDP in vivo on P388 leukemia whe n administered i.p. (intraperitoneal) on day 1. (C) 1997 Elsevier Scie nce Inc.