Biomedical subjects

T Klapötke

Publications and source records attributed to T Klapötke.

7 recordsLinked to original sources

PubMed1992

Ionic rhenocene derivatives with antitumor activity.

The antitumor activity of the three air-stable bis(cyclopentadienyl)rhenium derivatives [(C5H5)2-ReCl2]+Cl-,[(C5H5)2ReCl2]+[AsF6]- , and [(C5H5)2-ReCl2]+[SbF6]- was tested against Ehrlich ascites tumor in female CF1 mice. All three compounds contain the group-7 transition metal rhenium in the +5 oxidation state as their central metal atom. They are ionic, salt-like complexes that are composed of the cationic [(C5H5)2ReCl2]+ moiety and one of the negatively charged counterions Cl-, AsF6-, or SbF6-. Both the chloro and the hexafluoroarsenate complexes induced a maximal cure rate of 100% when given either in a dose range of 120-160 mg/kg (rhenocene trichloride) or at a single dose of 180 mg/kg (hexafluoroarsenate derivative). The hexafluoroantimonate complex effected a maximal cure rate of only 50% at 60 mg/kg. For the two former compounds, the values for the therapeutic index (TI) amounted to 1.7 and 2.1, respectively. No impairment of the general condition or pathologic symptoms in the viscera could be detected by observation of the animals during the days following treatment with therapeutic doses or by autopsy of the surviving animals on the key date (day 90). The rhenocene derivatives investigated in the present study represent a new class of antitumor metallocene compounds as well as the first rhenium(V) complexes exerting cytostatic activity.

Animals↗

PubMed1992

Antitumor activity of ionic niobocene and molybdenocene complexes in high oxidation states.

Four air-stable niobocene complexes [(C5H5)2NbCl2]+X- with X = BF4, AsF6, SbF6, SO3CF3 and the molybdenocene derivative [(C5H5)2MoCl2]2+[SbF6]2- were investigated for antitumor properties against Ehrlich ascites tumor in female CF1 mice. All compounds are new, salt-like complexes containing a cationic metallocene moiety, where the early transition metals niobium and molybdenum in the high oxidation states +5 and +6 function as central atoms. The niobocene complexes containing tetrafluoroborate (BF4-) or trifluoromethanesulfonate (CF3SO3-) as anions only induced a maximal cure rate of 50% and led to increases in life span of 182% and 178% following application of optimal doses. The other two niobocene compounds with hexafluoroarsenate (AsF6-) and hexafluoroantimonate (SbF6-) as anions and the molybdenocene derivative [(C5H5)2MoCl2]2+[SbF6]2- effected a maximal cure rate of 100% and increases in life span of 346%, 376%, and 332%, respectively, determined on the key date, i.e., on day 90 after transplantation. On applying the niobocene hexafluoroantimonate complex [(C5H5)2NbCl2] +[SbF6]-, the optimal dose range with a cure rate of 100% was rather broad and extended from 20 mg/kg to 40 mg/kg. Correspondingly, the value of the therapeutic index (TI) was high and amounted to 7.2. In the case of the niobocene hexafluoroarsenate and the molybdenocene hexafluoroantimonate complexes, the TI value decreased to 5.3 and 2.6 respectively. Neither impairments of the general condition nor any conspicuous symptoms could be detected after application of therapeutic doses of the five compounds investigated. Compared to the neutral niobocene dichloro complex [(C5H5)2NbCl2], the therapeutic range of the ionic niobocene derivative [(C5H5)2NbCl2]+[SbF6]- was broadened, the TI value markedly elevated from 2.9 to 7.2, and the toxic symptoms were impressively reduced. The niobocene hexafluoroantimonate complex was the most effective compound investigated in the present study.

Animals↗

PubMed1989

Ionic titanocene complexes: a new type of antitumor agent.

Five ionic cyclopentadienyltitanium (IV) derivatives were investigated for their activity against fluid Ehrlich ascites tumor. Four compounds were built up by the intact bis(cyclopentadienyl)titanium(IV) ("titanocene") unit, forming the cationic moiety together with two covalently bound ligands, with certain anions being bonded via electrostatic forces: the acetonitrile complex [(C5H5)2TiCl(NCCH3)]+[FeC14]- (I), the 2'2'-bipyridyl derivative [(C5H5)2Ti(bipy)]2+[CF3SO3]2 (II), the o-phenanthroline complex [(C5H5)2Ti(phen)]2+[CF3SO3]2 (III), and the N-methyl-o-aminothiophenolate derivative [(C5H5)2Ti[o-S(NACH3)C6H4]]+I- (IV). Another ionic cyclopentadienyltitanium derivative investigated was the five-coordinate bis(dithiolene) chelate (C5H5)Ti(1,2,4-S2C6H3CH3)2]-N(C2H5)4)+ (V), the cyclopentadienyltitanium moiety representing the anionic part of the complex salt. All complexes were ionic, salt-like compounds, distinguished by good water solubility. Whereas complexes I, III, and V, given at optimal dose levels, effected maximal cure rates of only 70%-80%, all animals were cured after receiving complexes II and IV at dose ranges of 200-220 and 240-300 mg/kg, respectively. The antitumor activity of complex I was confirmed against solid experimental tumor systems B16 melanoma, colon 38 carcinoma, and Lewis lung carcinosarcoma. Because of their improved solubility in water and pronounced antitumor activity (especially that of II and IV against fluid Ehrlich ascites tumor), ionic cyclopentadienyl titanium complexes are considered to be an interesting new type of antitumor agent.

Animals↗

PubMed1989

Antitumor activity of an ionic titanocene tetrachloroferrate derivative against some solid experimental tumors.

The metallocene complex bis(cyclopentadienyl)acetonitrilechlorotitanium(IV) tetrachloroferrate(III) [(C5H5)2Ti(Cl)NCCH3]+[FeCl4]- was investigated for antitumor properties against three solid experimental animal tumors (B16 melanoma, colon 38 adenocarcinoma, Lewis lung carcinosarcoma). The growth of all three tumors was inhibited significantly by the titanocene complex. Colon 38 carcinoma and Lewis lung carcinoma revealed to be more sensitive to the titanocene tetrachloroferrate derivative than solid B16 melanoma, whereby the growth development of the aforementioned tumors was suppressed by 70-76% of control tumor size to T/C ratios amounting to 24-30%. Bis(cyclopentadienyl)acetonitrilechlorotitanium(IV) tetrachloroferrate(III) is representative of ionic titanocene complexes which are generally distinguished by improved water solubility in comparison to neutral metallocene compounds.

Acetonitriles↗

PubMed1989

Tumor inhibition by ferricenium complexes. Activity against some solid experimental tumors.

In the present study, the antitumor activity of some water-soluble ferricenium complexes [(C5H5)2Fe]+ X- (I, X- = [FeCl4]-; II, X- = 1/2[Cl3FeOFeCl3]2-; III, X- = [2,4,6-(NO2)3C6H2O]-; IV, X- = [CCl3COO]- 2CCl3COOH) was investigated against the solid, subcutanteously growing tumors sarcoma 180, B16 melanoma and colon 38 adenocarcinoma. Whereas, in the case of solid sarcoma 180, only marginal antitumor activity was observed for I-IV, the compounds effected growth inhibitions of solid B16 melanoma and colon 38 carcinoma by 35-60% and 50-73%, respectively, resulting in T/C ratios of 40-65% and 27-50%. In most tests, ferricenium trichloroacetate IV, followed by ferricenium mu-oxo-bis(trichloroferrate) II, were characterized by best antitumor properties against the tumor models investigated.

Adenocarcinoma↗

PubMed1988

Biological activity of organometallic bismuth compounds.

The chemical aspects of organometallic bismuth(III) compounds are discussed with respect to the stability of the metal-carbon sigma bond, their low dipole moments, and the limited solubility of these complexes in hydrophilic solvents. A new Bi heterocycle, which is of potential interest in terms of stability and solution behaviour, was shown to exist as an intermediate under the conditions in the mass spectrometer. Although generally bismuth organic compounds are extremely toxic, in the 1970s they became important as biocides and this is still being investigated. They have also been discussed as irritation causing chemical warfare agents. While their application in chemotherapy never became very widespread because antibiotics were discovered, in the last few years the antitumor activity of some derivatives has been reported.

Animals↗

PubMedDate not supplied

Tumor inhibition by titanocene complexes: activity against sarcoma 180.

The antitumor activity of various titanocene derivatives was examined against ascitic and solid, subcutaneously growing sarcoma 180. The complexes investigated were two dihalide compounds, (C5H5)2TiCl2 (I) and (C5H5)2TiBr2 (II), two carboxylato complexes, (C5H5)2Ti (cis-OOCCH = CHCOOH)2(III) and (C5H5)2Ti(OOCCCl3)2(IV), and the p-aminothiophenolate hydrochloride (C5H5)2Ti(p-SC6H4NH3+Cl-)2(V). Against ascitic sarcoma 180, best results were obtained for I; an injection of 50 mg/kg resulted in the survival of 40-50% of the animals (ILS, 161-184%). A similar result was recorded for cis-diamminedichloroplatinum(II), whereas the compounds II-IV induced a maximum cure rate of 20% (ILS, 95-139%). Against solid sarcoma 180, triple injections of I-V caused reduction of mean tumor weight to 23-53% of control values, the dichloro complex I exhibiting most pronounced activity. These results clearly underline antitumor potency for titanocene complexes (C5H5)2TiX2 modified at the acido ligand X.

Animals↗