Effects of cisplatin and two novel palladium complexes on Candida albicans.

The effects of cisplatin and two novel palladium complexes of possible cancer chemotherapeutic value on the yeasts Candida albicans and Saccharomyces cerevisiae were studied. All three drugs had growth inhibitory effects. Significant effects on uridine uptake by all three drugs were seen, but inhibition of thymidine uptake was either small or non-existent. A marked stimulatory effect of all of the complexes on cell respiration was observed after 16 h growth in their presence. In some cases immediate stimulation of cellular respiration was invoked on drug treatment. The palladium complexes caused extensive mycelial growth of C. albicans whilst cisplatin induced pseudohyphal growth. Results are discussed with respect to possible mechanisms of action of the drugs.

Complexes of vitamin B6XX: equilibrium and mechanistic studies of the reaction of pyridoxal-5'-phosphate with pyridoxamine-5'-phosphate in the presence of copper(II).

The interaction of Cu(II) with pyridoxamine-5'-phosphate (PMP) and pyridoxal-5'-phosphate (PLP) was studied potentiometrically. The titration data were assessed by MINIQUAD program. Several protonated and nonprotonated complexes have been found to exist in solution. The reaction of PLP with Cu(II)-PMP has been studied kinetically, using the stopped-flow technique. Two rate steps have been observed. The first step has been attributed to the formation of a Schiff's base metal complex. The second step may be due to the formation of a ternary complex formation. A mechanism was suggested.

Complexes of hydroxamates. V: Equilibrium and kinetics of the formation of the binary and ternary complexes involved in the nickel(II)-histidinehydroxamic acid-pyridoxal system.

Equilibrium-based computer models utilizing SUPERQUAD program were made to determine the formation constants of the binary complexes of Ni(II) with histidine-hydroxamic acid (HX) from pH-metric titration data at 25 degrees C and I = 0.15 M NaCl. The species were monomeric in the pH range 3.0-8.0. The mechanism of their complex formation was determined using the stopped flow technique under the same experimental conditions of the equilibrium study. It has been concluded that Ni2+ and NiOH- were the active species in the complex formation reactions. Moreover, the reaction of HX with pyridoxal (PL) was studied in the absence of metal-ions by polarographic and spectrophotometric techniques at pH greater than or equal to 5.0. No rates were observed by using the stopped-flow methods. The formation constants for the binary system (HX-PL) and the ternary system (Ni(II)-HX-PL) were also determined by the same program applied on data obtained from pH metric titration at 25 degrees C and I = 0.15 M NaCl. Ternary complex formation involving PL and the species of the Ni(II)-HX system was also investigated kinetically in the pH range of 6.5-10.5. Several rate steps have been observed which have been interpreted qualitatively in terms of sequence of processes involving the condensation of aldehydic form of PL with amino moiety of HX. A comparison with other pertinent systems is also discussed.

Preliminary studies on the inhibitory effect of novel Pd(II) complexes of vitamin B6 on cell divisions.

Two novel complexes of Pd(II) involving vitamin B6 compounds have been synthesized. They are compatible with the compositions Pd(P.H.)2 C2(P = pyridoxol) and Pd(PL.H)2 C2(PL = pyridoxal). The complexes inhibited the growth as well as the biosynthesis of RNA, DNA, and protein of E. coli B-766. Photoacoustic spectral (PAS) measurements showed that the complexes bound to DNA of the bacteria and were present only in the kidney of treated mice. The complexes inhibited the incorporation of 3H-thymidine as well as 14C-leucine in the DNA and protein, respectively, of liver cell cultures (BL8L). The inhibition of cell division of Walker-S-cells and human lymphocytes by the complexes was highly significant.