Synthesis, characterization and cytotoxicity of new platinum(IV) axial carboxylate complexes: crystal structure of potential antitumor agent [PtIV(trans-1R,2R-diaminocyclohexane)trans(acetate)2Cl2].
A series of new platinum(IV) complexes of the type [PtIV(DACH)trans(L)2Cl2] (where DACH = trans-1R,2R-diaminocyclohexane, and L = acetate, propionate, butyrate, valerate, hexanoate, or heptanoate) bearing the carboxylate groups in the axial positions have been synthesized and characterized by elemental analysis, IR, and 195Pt NMR spectroscopy. The crystal structure of the analogue [PtIV(DACH)trans(acetate)2Cl2] was determined by single crystal X-ray diffraction method. There were two crystallographically independent molecules, both of which lie on crystallographic two-fold axes. The bond lengths and bond angles of both the molecules were the same within the experimental error. The compound crystallizes in the monoclinic space group C2, with a = 11.180(2) A, b = 14.736(3) A, c = 10.644(2) A, beta = 112.38(3) degrees, Z = 4 and R = 0.0336, based upon a total of 1648 collected reflections. In this complex, the platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogens of DACH, whereas the other two equatorial positions were occupied by two chloride ions. The remaining two axial positions were occupied by the oxygens of acetate ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. These analogues were evaluated in vitro and demonstrated cytotoxic activity against the human ovarian 2008 tumor cell line (IC50 = 0.001-0.06 microM). Structure-activity study revealed that activity was highest for the analogue where L = butyrate.
Ali Khan
S R
SR
Department of Clinical Investigation, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Huang
S
S
Shamsuddin
S
S
Inutsuka
S
S
Whitmire
K H
KH
Siddik
Z H
ZH
Khokhar
A R
AR
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010984:Platinum; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C119451:(diaminocyclohexane)(diacetato)(dichloro)platinum; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D009944:Organoplatinum Compounds; D010984:Platinum; D002945:Cisplatin