Synthesis and antitumor activity of the metformin platinum (IV) complex. Crystal structure of the tetrachloro(metformin)platinum (IV) dimethylsulfoxide solvate.
The synthesis of (metformin) tetrachloroplatinum (IV) was investigated (metformin is N,N-dimethylbiguanide). It crystallizes with one dimethylsulfoxide molecule as solvate in the monoclinic system, space group P2(1)/n (No. 14) with Z = 4. The cell dimensions are: a = 13.136(7), b = 9.424(2), c = 14.009(8) A, beta = 111.96(4) degrees, V = 1608.4(2) A3. Of the 4269 independent nonzero reflections collected, 1979 with I > 3 sigma (I) were considered and used in the calculations. The structure was refined to R = 0.043 and wR = 0.045. The platinum coordination is octahedral, built up from four chloride anions and one bidentate chelating ligand via the two imine nitrogen atoms cis position. The distances and angles are typical of six-membered rings that have similar donor atoms. The complex was evaluated in vitro and in vivo on murine P388 leukemia. It was found to be as potent as cis-dichlorodiammine 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 compounds induced a similar perturbation in the G2+M phases of the cell-cycle. The complex was less active than CDDP in vivo on P388 leukemia when administered i.p. (intra peritoneal) on day 1.
Bentefrit
F
F
Laboratoire de Chimie Physique, Minérale et bioinorganique, Faculté de Pharmacie, Université de Paris Sud, Châtenay-Malabry, France.
Morgant
G
G
Viossat
B
B
Leonce
S
S
Guilbaud
N
N
Pierre
A
A
Atassi
G
G
Nguyen
H D
HD
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D008687:Metformin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C108657:tetrachloro(metformin)platinum(IV); D008687:Metformin