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Biomedical subjects

Y Kidani

Publications and source records attributed to Y Kidani.

At least 55 records · Page 3Linked to original sources

Coordination chemical studies on metalloenzymes. IX. Properties of the ternary complex between cobalt(II)-bovine carbonic anhydrase and bidentate ligands.

The spectrum, thermodynamic parameters, and proton longitudinal relaxation time of the ternary complex between various bidentate ligands (2-pyridinecarboxylate, 2-quinolincarboxylate, 8-quinolinecarboxylate, and 2-pyridylacetate) and cobalt(II)-bovine carbonic anhydrase were measured to clarify the nature of the ternary complex. The formation constants of the ternary complexes of bidentate ligands are in the order of (2-pyridinecarboxylate approximately greater than 8-quinolinecarboxylate much greater than 2-quinolinecarboxylate approximately equal to 2-pyridylacetate). The degree of the shift of the band characteristic of five-coordinate species at 13-15 kcm-1 (cm-1 X 10(-3)) and that of the higher energy band at 21-22 kcm-1 decrease almost in the same order. These results are explained on the basis of the contribution of the bond formation between the nitrogen atom of the heterocyclic ring of ligands and cobalt ion. The formation constants of the ternary complex of bidentate ligands were compared to the stability constants of various ligands with a cobalt ion but there is no correlation in these values. The rate constant of break-up of the ternary complex was discussed on the coordination geometry of the ternary complex on the basis of the degree of the distortion.

Animals↗

Relation of conformation to antitumor activity of platinum(II) complexes of 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine isomers against leukemia P388.

The antitumor activity of various platinum(II) complexes of 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine isomers against leukemia P388 was evaluated by means of the platinum analogue study protocol recommended by the National Cancer Institute. For the former complexes, trans isomers are more efficacious than the corresponding cis isomers. For the latter complexes, cis isomers seem to be somewhat more active than trans isomers. 2-(Aminomethyl)cyclohexylamine platinum complexes exhibited higher activity than 1,2-cyclohexanediamine complexes in this tumor system. These findings encouraged us to determine the structural differences between 1,2-cyclohexanediamine and 2-(aminomethyl)cyclohexylamine complexes. Their structures of platinum complexes were elucidated from circular dichroism and 13C NMR spectral analyses, and it has been concluded that the cyclohexane ring of cis-1,2-cyclohexanediamine is nearly perpendicular to the chelate ring, while both rings of trans-1,2-cyclohexanediamine and trans-2-(aminomethyl)cyclohexylamine complexes lie in a common plane. The structure of cis-2-(aminomethyl)cyclohexylamine complexes is flexible, and the cyclohexane ring is not perpendicular to the chelate ring. The coplanarity of trans isomers and the flexibility of cis-2-(aminomethyl)cyclohexylamine complexes allow them easy approach to the target DNA. However, the perpendicular ring of cis-1,2-cyclohexanediamine complexes would prevent their interactions with dna molecules due to the steric hindrance.

Animals↗

Effects of anticancer platinum compounds on Escherichia coli strains with normal and defective DNA repair capacity.

The effect of anticancer platinum compounds on isogenetic strains of Escherichia coli with normal or defective DNA repair capacity were studied. Cisdichlorodiammineplatinum (II) causes DNA damage that is repairable by the repair systems of bacteria, and the DNA lesion becomes mutational when processed by the excision repair system. Dinitrato (1R, 2S-cyclohexanediamine) platinum (II) exhibits similar killing activity on E. coli strains with both normal and defective DNA repair capacity. Thus, this compound may cause DNA damage that cannot be repaired by bacteria, or its killing activity may be due to effects other than DNA damage.

Antineoplastic Agents↗

Metal coordination geometry of ternary complex between cobalt-bovine carbonic anhydrase and multidentate ligands.

Interaction of cobalt(II) bovine carbonic anhydrase with 3- and 4-pyridinecarboxylates, 2-pyridinecarboxylate, and 2,6-pyridinedicarboxylate has been investigated by the spectrophotometric method. The apparent formation constant of the ternary complex (ligand : cobalt ion : apoenzyme = 1 : 1 : 1) was determined from spectral data. The spectroscopic data of the ternary complex indicate that the 3- or 4-pyridinecarboxylate adduct has a five-coordination geometry through three donor atoms of the protein part of the enzyme, the carboxyl group of 3- or 4-pyridinecarboxylate, and a water molecule. 3- or 4-Pyridinecarboxylate behaves as a monodentate ligand. The spectrum of the ternary complex of 2-pyridinecarboxylate was very different from that of 3- or 4-pyridinecarboxylate. The spectra data indicate that 2-pyridinecarboxylate adduct has a five-coordination geometry and that it behaves as a bidentate ligand. The ternary complex of 2,6-pyridinedicarboxylate was so unstable that the spectrum of the ternary complex was determined by the indirect method. The spectrum of 2,6-pyridinedicarboxylate adduct shows lower molar absorption than that of 2-pyridinecarboxylate adduct. This result indicates that 2,6-pyridine dicarboxylate behaves possibly as a tridentate ligand.

Animals↗

Antitumor activity of platinum(II) complexes of 1,2-diamino-cyclohexane isomers.

Dichloro, dibromo, oxalato, malonato, dinitrato, sulfato and mono and bis-(D-glucuronato) platinum(II) complexes of 1,2-diaminocyclohexane (dach) isomers were prepared and tested on L1210 mouse leukemia employing the NCI protocol for evaluation of Pt analogs. A large number of long-term survivors were observed with certain analogs, though the therapeutic indices (optimal dose/minimum effective dose) were not large. Among the analogs tested, the oxalato, malonato, dinitrato and mono-(D-glucuronato) Pt(II) complexes of trans-1,2-diaminocyclohexane were found to be particularly effective. The glucuronato Pt complexes appear to be promising candidates for clinical trial since they have the highest solubility in water.

Animals↗

Binding sites between platinum (II) and uracil derivatives.

The complexes of triammineplatinum with uracil, 6-methyluracil, or uridine were prepared in aqueous solution at pH 7. The reaction of uracil with triammineplatinum gave two complexes at the same time. One was a complex in which triammineplatinum displaced a proton from uracil and coordinated to the N(3) position, and the other the complex coordinated to the N(1) position by displacing a proton. When triammineplatinum was treated with 6-methyluracil or uridine in aqueous solution at pH7, only a complex coordinated to the N(3) position was obtained. The ultraviolet (UV), NMR, and infrared (IR) spectral data provide useful information for determining the binding site of these complexes. The UV and IR spectral behaviors of the complex coordinated to the N(3) of uracil are very similar to those of 3-methyluracil. The NMR spectrum of the complex coordinated to the N(1) of uracil exhibits satellite peaks of 195Pt-proton and its coupling constant (39 Hz) gives good evidence for determining the binding site at the N(1) position.

Chemical Phenomena↗

Antitumor activity of 1,2-diaminocyclohexane--platinum complexes against sarcoma-180 ascites form.

Platinum complexes derived from three isomers of 1,2-diaminocyclohexane have been synthesized and their antitumor activities were evaluated against ascites Sarcoma-180. All the platinum complexes had high antitumor activity. Platinum complexes derived from cis-1,2-diaminocyclohexane were more effective than those derived from trans-l-and trans-d-1,2-diaminocyclohexane. Among the platinum complexes tested, oxalato(cis-1,2-diminocyclohexane)platinum had a remarkably high therapeutic index. Modification of the nonleaving group as well as that of the leaving group is important in order to find better antitumor platinum complexes.

Animals↗

Antitumor activity of water-soluble platinum(II) complexes of 1,2-cyclohexanediamine isomers.

Dichloroplatinum(II) complexes of 1,2-cyclohexanediamine isomers were reported to have high antitumor activity against leukemia L-1210 and P-388, but they were hardly soluble in water and, therefore, dibromo- and diiodo-platinum(II) complexes of 1,2-cyclohexanediamine isomers were prepared. They were not soluble in water but showed high antitumor activity. When the chloride ions are replaced with sulfate ions, they become soluble and also they are anti-tumor active. Bismonobromoacetatoplatinum (II) complexes were synthesized and tested. Mono- and bis-(D-glucuronato)platinum(II) complexes of 1,2-cyclohexanediamine isomers were newly synthesized. All of them were freely soluble in water and showed high antitumor activity with low toxicity. The chelated mono(D-glucuronato)platinum(II) was found to be more effective than the monodentate bis(D-glucuronato)platinum (II) complexes.

Animals↗