Prolactin and aggression in women with fertility problems.

This study tested the hypothesis that women with higher prolactin feel more hostility, anger and aggression. A total of 66 women with moderate fertility problems were grouped into the 50% who had the highest and the 50% who had the lowest levels of prolactin. Levels of hostility, aggression and anger were compared. Women with higher prolactin levels did not report significantly increased hostility. After Bonferroni correction, women with lower prolactin showed non-significantly increased scores on two measures of state anger, and on a measure of trait temper. When comparing those with the highest and lowest 20% of prolactin levels, those with lower prolactin had non-significantly higher scores on trait temper and outward expression of anger, and non-significantly lower scores for control of anger. Although non-significant, these findings run counter to those of earlier studies on this topic. Implications for future research and patient care are discussed.

Visual-spatial cognition in women with polycystic ovarian syndrome: the role of androgens.

STUDY QUESTION: Are women with polycystic ovary syndrome (PCOS) better at three-dimensional mental rotation than other women? SUMMARY ANSWER: Women with PCOS scored significantly higher on a mental rotation task than a female control group. WHAT IS KNOWN ALREADY: PCOS is a condition characterized by elevated testosterone levels. Some researches have found that three-dimensional mental rotation task performance is positively correlated with testosterone levels. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted between June 2006 and January 2009. The participants were 69 women with PCOS and 41 controls recruited from five gynaecology clinics in London. The control group consisted of non-PCOS women of comparable subfertility to PCOS group. These groups sizes gave roughly 80% power to detect moderate effect sizes for the main statistical test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were recruited at London gynaecology clinics. The women were aged between 18 and 43. PCOS was diagnosed based on the Rotterdam criteria. Controls were women who experienced some degree of subfertility. Blood samples from participants were frozen for up to 4 months until being assayed by direct electrochemiluminescence. The mental rotation task was undertaken electronically. Some questionnaires and other tasks were completed as control measures. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS scored significantly higher than controls: median (range) 3.00 (0-9) and 2.00 (0-8), respectively (U = 1147.500, N1 = 69, N2 = 41, P < 0.047). Within the PCOS group, circulating levels of testosterone were significantly positively correlated with three-dimensional scoring (rs = 0.376, n = 56, P < 0.002), whereas estradiol was significantly negatively correlated with three-dimensional scoring (rs = -0.473, n = 29, P < 0.010). In the control group, the relationship between sex hormones and mental rotation was non-significant. Other factors, including general intelligence and social class, did not account for these findings. A subgroup analysis comparing hyperandrogenic PCOS cases, non-hyperandrogenic PCOS cases and controls, in which age and body mass index were controlled for using ANCOVA, found a non-significant difference in three-dimensional scoring between the three groups (F = 1.062, d.f. = 1, 73, P < 0.351). LIMITATIONS, REASONS FOR CAUTION: The small number of women in the control group meant that correlations were underpowered in this group. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to find a benefit of PCOS in visuospatial cognition, and the first to find a link between visuospatial cognition and sex hormones in PCOS. The fact that the correlations went in the opposite direction in the PCOS group compared with the controls might suggest the influence of increased prenatal exposure to androgen in PCOS. STUDY FUNDING/COMPETING INTEREST(S): The assays for this study were funded by the Department of Psychology, City University London. All authors report no conflicts of interest.

Synthesis and biological evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives.

3-(4-Chlorophenyl)-4-substituted pyrazole derivatives were synthesised and tested for their in vitro antifungal activity. Some compounds showed very good antifungal activity against four pathogenic strains of fungi. The same compounds exhibited an interesting activity against the tested strain of Mycobacterium tuberculosis H37Rv. The results suggest that 1,3,4-oxadiazoles and 5-pyrazolinones bearing a core pyrazole scaffold may be promising antifungal and antitubercular agents.

Iontophoresis-mediated transdermal permeation of peptide dendrimers across human epidermis.

PURPOSE OF THE STUDY: The overall aim of the present work was to elucidate the effects of iontophoresis on assisting permeation/deposition of peptide dendrimers across/within human skin. PROCEDURES: A series of peptide dendrimers containing arginine and histidine as terminal acids were synthesized and characterized. These dendrimers were subjected to passive and iontophoretic permeation studies across human epidermis. RESULTS: The synthesized peptide dendrimers were found to be stable in epidermal, dermal and skin extracts up to 6 h. Passive diffusion studies revealed that none of the synthesized peptide dendrimers permeated human epidermis up to 6 h, although minute concentrations of low molecular weight dendrimers were detected in receptor medium at the end of 24 h. Application of iontophoresis significantly increased the permeation of all the tested peptide dendrimers across human skin in a molecular weight-dependent manner compared to simple passive diffusion. Electromigration was found to be the dominant mechanism behind the iontophoretic permeation of peptide dendrimers across human skin. CONCLUSIONS: The present study demonstrates that iontophoresis is an effective technique in enhancing the transdermal permeation of peptide dendrimers. MESSAGE OF THE PAPER: This study foresees the possibility of applying peptide dendrimers in iontophoretic delivery of drugs and macromolecules across/within the skin.

Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives.

As a part of our research to develop novel antitubercular and antimicrobial agents, a series of 3-(4-chlorophenyl)-4-substituted pyrazoles have been synthesised. These compounds were tested for antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system, antifungal activity against a pathogenic strain of fungi and antibacterial activity against gram-positive and gram-negative organisms. Among them tested, many compounds showed good to excellent antimicrobial and antitubercular activity. The results suggest that hydrazones, 2-azetidinones and 4-thiazolidinones bearing a core pyrazole scaffold would be potent antimicrobial and antitubercular agents.

Yellow nail syndrome following thoracic surgery: a new association?

An 80-year-old man presented with the characteristic triad of yellow nail syndrome (chronic respiratory disorders, primary lymphedema and yellow nails) in association with coronary artery bypass graft surgery. Treatment with mechanical pleurodesis and vitamin E resulted in near complete resolution of the yellow nails, pleural effusions, and lower extremity edema. The etiology of the yellow nail syndrome has been described as an anatomical or functional lymphatic abnormality. Several conditions have previously been described as associated with this disease. This is the first report of the association of this syndrome with thoracic surgery.

The DNA strand of chimeric RNA/DNA oligonucleotides can direct gene repair/conversion activity in mammalian and plant cell-free extracts.

Chimeric oligonucleotides (chimeras), consisting of RNA and DNA bases folded by complementarity into a double hairpin conformation, have been shown to alter or repair single bases in plant and animal genomes. An uninterrupted stretch of DNA bases within the chimera is known to be active in the sequence alteration while RNA residues aid in complex stability. In this study, the two strands were separated in the hope of defining the role each plays in conversion. Using a series of single-stranded oligonucleotides, comprised of all RNA or DNA residues and various mixtures, several new structures have emerged as viable molecules in nucleotide conversion. When extracts from mammalian and plant cells and a genetic readout assay in bacteria are used, single-stranded oligonucleotides, containing a defined number of thioate backbone modifications, were found to be more active than the original chimera structure in the process of gene repair. Single-stranded oligonucleotides containing fully modified backbones were found to have low repair activity and in fact induce mutation. Molecules containing various lengths of modified RNA bases (2'-O-methyl) were also found to possess low activity. Taken together, these results confirm the directionality of nucleotide conversion by the DNA strand of the chimera and further present a novel, modified single-stranded DNA molecule that directs conversion in plant and animal cell-free extracts.

The differential expression of cytokeratin 18 in cisplatin-sensitive and -resistant human ovarian adenocarcinoma cells and its association with drug sensitivity.

DNA is the primary target of cis-diamminedichloroplatinum (cisplatin), but the drug also interacts with the cellular cytoskeleton composed of microtubules and intermediate filaments. It was found that the cisplatin-resistant 2008/C13* cell line contained markedly lower levels (6-fold) of cytokeratin 18, when compared to the cisplatin-sensitive 2008 cell line. Northern blot analysis revealed a markedly decreased level of cytokeratin 18 mRNA in the resistant cell line. Southern blot analysis of the DNA extracted from the two cell lines and then digested with HpaII and its methylation-sensitive isoschizomer, MspI, revealed no detectable differences in the methylation status of the cytokeratin gene. Neither 5-azacytidine (5 microM) nor retinoic acid (1 microM) treatment enhanced the expression of cytokeratin 18 in the resistant cell line. However, transfection of full-length cytokeratin 18 cDNA into the cisplatin-resistant 2008/C13* cells resulted in clones with increased levels of cytokeratin 18, which was accompanied in the majority of clones by a marked increase in their sensitivity to cisplatin. These results demonstrate that modulating the expression of an intermediate filament protein results in sensitization of a drug-resistant human ovarian cell line to cisplatin.

Expression of the cisplatin resistance phenotype in a human ovarian carcinoma cell line segregates with chromosomes 11 and 16.

Many mechanisms have been proposed to explain cisplatin resistance, suggesting that this phenomenon is multifactorial. In an attempt to define the chromosome(s) responsible for cisplatin resistance in the human ovarian carcinoma 2008/C13* cell lines, somatic cell hybrids were obtained following fusion of the cisplatin-resistant 2008/C13* cells with an A9 rodent fibroblast cell line. The hybrids were then analyzed for segregation of the human chromosomes with the drug-resistant phenotype. Chromosomes 11 and 16 were present in all of the resistant somatic cell hybrids, with the highest concordance for chromosome 16. The role of both of these chromosomes was further established with microcell hybrids. Microcell hybrids of A9 cells with chromosome 16 from the 2008/C13* cells did not exhibit cisplatin resistance, but the presence of a normal chromosome 11 with chromosome 16 (derived from cisplatin-resistant 2008/C13* cells and not from the cisplatin-sensitive 2008 cells) resulted in increased resistance to cisplatin. In addition, loss of chromosome 11 from a resistant somatic cell hybrid resulted in the hybrid becoming sensitive to cisplatin, implicating this chromosome in maintaining the resistant phenotype. The results demonstrate that resistance to cisplatin is a dominant trait in the 2008/C13* human ovarian cells, and both chromosomes 11 and 16 are required for its expression.

Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-gamma.

Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-glycoprotein (P-gp), an alteration in the levels of beta-tubulin isotypes, and/or changes in the drug binding affinity of the microtubules. We established two paclitaxel-resistant human ovarian carcinoma cell lines. The 2008/17/4 cells exhibited a "classic" multidrug-resistant phenotype (overexpression of P-gp associated with cross-resistance to natural product drugs), whereas the 2008/13/4 cells were an atypical multidrug-resistant subline (no overexpression of P-gp). In addition to being paclitaxel resistant (250-fold), the 2008/13/4 cells were also cross-resistant to etoposide (39-fold) and vincristine (460-fold). To identify the alterations in the gene expression profile associated with the development of atypical paclitaxel resistance, we used the Clontech Atlas Human Cancer cDNA Microarray (spotted with 588 genes). The expression of retinoic acid receptor (RAR)-gamma was significantly higher in the paclitaxel-resistant (2008/13/4 and 2008/17/4) cells than in the parental (2008) cells. Northern blotting analysis demonstrated that the expression of RAR-gamma was 7-fold higher in the 2008/13/4 and 2008/17/4 cells than in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line. Whereas the 2008, 2008/13/4, and 2008/17/4 cells were found to resist the antiproliferative effects of all-trans-retinoic acid, the paclitaxel-resistant cells were 6- to 7-fold cross-resistant to the antiproliferative effects of CD437 (a synthetic RAR-gamma-selective agonist; 6-[-(1-admantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid) compared with the sensitivity of the parental cells. To further understand the association of paclitaxel and CD437 resistance with the observed RAR-gamma overexpression, we transfected the 2008 cells with a full-length RAR-gamma cDNA construct. Two transfectants with increased expression of the RAR-gamma mRNA and protein were isolated and subjected to growth inhibition assays in the presence of various concentrations of paclitaxel, etoposide, vincristine, and CD437. The sensitivity of the 2008 transfected clones (displaying increased expression of RAR-gamma) to the cytotoxic effects of paclitaxel, etoposide, vincristine, and CD437 was similar to that observed in the parental 2008 cells. These results suggest that the overexpression of RAR-gamma (observed in the 2008/13/4 and 2008/17/4 cells) by itself is not capable of inducing paclitaxel and CD437 resistance (or resistance to etoposide and vincristine).

Prevalence of the APOC3 promoter polymorphisms T-455C and C-482T in Asian-Indians.

Potential mechanisms accounting for the high cardiovascular death rates observed in Asian-Indians are dyslipidemia and insulin resistance. Polymorphisms in the APOC3 promoter (-455 T/C and -482 C/T) were frequently encountered in young Asian-Indians and they correlated with reduced concentrations of apolipoprotein A-I.

Circumvention of adriamycin resistance: effect of 2-methyl-1,4-naphthoquinone (vitamin K3) on drug cytotoxicity in sensitive and MDR P388 leukemia cells.

The effect of vitamin K3 (2-methyl-1,4-naphthoquinone) on Adriamycin (ADR) induced growth inhibition of drug sensitive and multidrug resistant P388 leukemia cells was evaluated. Exposure to ADR concentrations of 100-5000 ng simultaneously with 1 microM vitamin K3 elicited an enhanced inhibition of tumor cell survival. The effect of treatment with ADR alone, or in combination with vitamin K3 on DNA and RNA biosynthesis in the sensitive and resistant tumor cells, was also assessed. DNA and RNA biosynthesis inhibition was increased in P388/S (the parental cell line) and P388/ADR cells (the ADR resistant cell line which exhibits the multidrug resistant (MDR) phenotype) exposed to ADR after pretreatment for 3 h with vitamin K3. Concurrent administration in vivo of vitamin K3 and ADR illustrated a therapeutically significant increase (P less than 0.05) in the life span of sensitive and resistant tumor cell bearing animals. Vitamin K3 caused a depletion of the intracellular glutathione (GSH) levels in P388/S and P388/ADR leukemia cells but at concentrations greater than those that enhanced ADR cytotoxicity. Pretreatment of the tumor cells with 1 microM vitamin K3 induced a 35-50% (P less than 0.001) elevation in the intracellular ADR accumulation in MDR P388 leukemia cells, while such an effect was absent in P388/S tumor cells. DNA binding studies performed utilizing calf thymus DNA, indicated that vitamin K3 enhanced the intercalation potential of ADR and also altered the equilibrium between the free and bound form of ADR in a cell free system. These factors and their possible effects on the potentiation of ADR cytotoxicity and the therapeutic significance of utilizing vitamin K3 as an adjuvant in the chemotherapy of MDR tumors is discussed.

Species-specific differences in taxol transport and cytotoxicity against human and rodent tumor cells. Evidence for an alternate transport system.

The efficacy of taxol against a wide range of sensitive and refractory solid tumors has prompted extensive investigation into the factors that influence its cytotoxicity. Our preliminary observations indicated that taxol had a superior antitumor effect against human cells (Daudi, K562, 2008, 2008/C13*, 2780 and C70) compared with its effect against rodent cells (WS, WR, NIH3T3, and CHO). Although verapamil, an inhibitor of P-glycoprotein function, markedly increased the efficacy of taxol against the rodent cells (WS, WR, and CHO), the expression of P-glycoprotein was found only at low levels in the WR cells. In addition, levels of the multidrug resistance-associated protein (MRP), as assessed by reverse transcriptase-polymerase chain reaction analysis, were found to be higher in the human than in the rodent cells, although MRP mRNA was not detected by northern blotting. Transport studies indicated that the reduced sensitivity of the rodent cells to taxol was due to decreased intracellular taxol levels and reduced intracellular binding. However, no correlation was found between the intracellular binding of taxol and the intracellular levels of alpha- and beta-tubulin, or the intracellular concentration of polymerized tubulin. These studies were extended further by assessing the binding of taxol to semi-purified microtubule proteins from WS, CHO and 2008/C13* cells in vitro. The microtubule protein preparations from WS, CHO and 2008/C13* cells, which have a 50-fold difference in their sensitivity to taxol, were found to bind equal amounts of radiolabeled taxol, and this binding was inhibited (80%) in the presence of unlabeled taxol. These results lead us to propose the presence in the rodent cells of an alternative taxol transport system that is distinct from the P-glycoprotein and MRP systems.

Acquisition of taxol resistance via P-glycoprotein- and non-P-glycoprotein-mediated mechanisms in human ovarian carcinoma cells.

Taxol-resistant clones from a human ovarian carcinoma cell line (2008) were selected by an initial exposure to 0.05 microM (2008/13) or 0.5 microM (2008/17) taxol. Thereafter, a series of clones with increasing taxol resistance were derived from the 2008/17 and 2008/13 cells by stepwise sequential exposure to increasing concentrations of taxol. The 2008/17 clones displayed a classical P-glycoprotein-mediated drug-resistance phenotype. In contrast, the 2008/13 clones followed the classical P-glycoprotein-mediated resistance phenotype until a 245-fold taxol-resistant clone (2008/13/2) was obtained, which was followed by a further increase in the degree of resistance but significant down-regulation of P-glycoprotein expression in the 252-fold taxol-resistant 2008/13/4 cells. This clone (2008/13/4) also accumulated significantly higher intracellular levels of taxol than those expressing the P-glycoprotein. No correlation between the expression of the multidrug resistance-associated protein and taxol resistance was observed. Verapamil increased the sensitivity of all drug-resistant clones to taxol, and this was probably related to the ability of verapamil to increase the intracellular concentration of taxol (except in the case of 2008/13/4 cells). The 2008/17 clones were highly cross-resistant to Adriamycin, etoposide, and vincristine. They also displayed a low level of cross-resistance to camptothecin but were not cross-resistant to cisplatin. The taxol-resistant 2008/13 clones displayed a similar pattern of cross-resistance for all drugs (except Adriamycin). The 2008/13 clones were only 2-to 4-fold cross-resistant Adriamycin. The levels of alpha-tubulin and beta-tubulin were similar in the parental 2008 and taxol-resistant 2008/13/4 cells. Furthermore, the in vitro binding of [3H]taxol to semipurified microtubule preparations derived from the parental 2008 and the taxol-resistant 2008/13/2 and 2008/13/4 cells was similar. These results show that in human ovarian carcinoma cells resistance to taxol can be acquired via as yet undescribed mechanisms.

NADPH-dependent enzyme-catalyzed reduction of aldophosphamide, the pivotal metabolite of cyclophosphamide.

One of the metabolites found in the urine of mammals given the prodrug cyclophosphamide is alcophosphamide, an alcohol. It is most probably generated from cyclophosphamide via aldophosphamide, an aldehyde which otherwise can directly give rise to phosphoramide mustard; the latter effects the cytotoxic action of cyclophosphamide and other oxazaphosphorines. It has already been demonstrated that horse liver alcohol dehydrogenase catalyzes the reduction of aldophosphamide to alcophosphamide. Herein, we report that aldose reductase and aldehyde reductase purified from human placenta also catalyze this reaction. The Km values for aldose reductase- and aldehyde reductase-catalyzed reduction of aldophosphamide to alcophosphamide were 0.15 and 1.6 mM, respectively. Aldose reductase and aldehyde reductase accounted for 94 and 6%, respectively, of total placental pyridine nucleotide-dependent enzyme-catalyzed aldophosphamide (160 microM) reduction. Aldose reductase-catalyzed reduction of aldophosphamide appeared to be noncompetitively inhibited by sorbinil; the Ki value was 0.4 microM. The in vivo significance of these observations is uncertain but could be of some magnitude since alcophosphamide is known to be only weakly cytotoxic.

Cross-resistance and collateral sensitivity to natural product drugs in cisplatin-sensitive and -resistant rat lymphoma and human ovarian carcinoma cells.

The cytotoxicity of mitotic spindle poisons, vinca alkaloids and the anthracycline, adriamycin, against cisplatin-sensitive and -resistant rat lymphoma and human ovarian carcinoma cell lines was investigated. Interestingly, it was found that all cell lines were more sensitive to the mitotic spindle poisons, vincristine and vinblastine. Adriamycin was the least effective and taxol had intermediate activity. The Walker rat lymphoma cell line resistant to cisplatin (WR) exhibited the multiple drug resistance phenotype since it showed collateral resistance to all drugs (ranging from twofold to taxol, colcemid and colchicine and sixfold to the vinca alkaloids). Verapamil potentiated the cytotoxic activity of adriamycin and vincristine in a striking fashion with the Walker cells. P-glycoprotein was found to be present in the plasma membranes of the Walker cells with approximately a 2.5-fold increase in the WR as compared to the sensitive (WS) cells. Glutathione levels were elevated in all of the cisplatin-resistant cell lines when compared to the cisplatin-sensitive parental cell lines. A profound effect of buthionine sulfoximine pretreatment on adriamycin cytotoxicity was observed. Glutathione S-transferase (pi) was present in all the human cell lines but the WS cells had markedly lower levels (almost negligible) when compared to the WR cells. These observations imply that cisplatin-resistant cells may be more sensitive to mitotic spindle poisons and vinca alkaloids, irrespective of the mechanism of platinum resistance, and that the cytotoxicity of vinca alkaloids could be further modulated by verapamil, irrespective of the presence or absence of P-glycoprotein.

Compression of the C-2 root by a rare anomalous ectatic vertebral artery. Case report.

The authors report a symptomatic congenitally anomalous ectatic vertebral artery not passing through the transverse foramen of the atlas (C-1), but instead piercing the dura mater below the posterior arch of the C-1 in the atlantoaxial (C1-2) interlaminar space. This occurrence is exceptionally rare, but in this case it was uniquely associated with occipital neuralgia due to vascular compression of the C-2 root. Microvascular decompression was curative. Neuroradiological and surgical findings are presented and their implications discussed.

Synthesis, characterization, DNA binding, and cytotoxic studies of some mixed-ligand palladium(II) and platinum(II) complexes of alpha-diimine and amino acids.

The syntheses of nine palladium(II) complexes of type [Pd(phen)(AA)]+ (where AA is an anion of glycine, L-alanine, L-leucine, L-phenylalanine, L-tyrosine, L-tryptophan, L-valine, L-proline, or L-serine) have been achieved. These palladium(II) complexes have been characterized by ultraviolet-visible, infrared, and 1H NMR spectroscopy. The binding studies of several complexes [M(NN)(AA)]+ (where M is Pd(II) as Pt(II), NN is 2,2'-bipyridine or 1,10-phenanthrodine, and AA is an anion of amino acid) with calf thymus DNA have been carried out using UV difference absorption and fluorescence spectroscopy. The mode of binding of the above complexes to DNA suggests the involvement of the hydrogen bonding between them. Several complexes [M(phen)(AA)]+ (where M is Pd(II) or Pt(II) and AA is an anion of amino acid) have also been screened for cytotoxicity in P388 lymphocytic cells. Of them, only two complexes, [Pd(Phen)(Gly)]+ and [Pd(phen)(Val)]+, show comparable cytotoxicity, as cisplatin does.

Synthesis, characterization, and cytotoxic studies of alpha-diimine/1,2-diamine platinum(II) and palladium(II) complexes of selenite and tellurite and binding of some of these complexes to DNA.

Eleven new complexes of formula [M(NN)(XO3)] (where M is Pd(II) or Pt(II); NN is 2,2'-bipyridine, 1,10-phenanthroline, 2,2'-dipyridylamine, ethylenediamine or (+-)trans-1,2-diaminocyclohexane, and XO3(2-) is SeO3(2-) or TeO3(2-)) have been synthesized. These water soluble complexes have been characterized by chemical analysis and conductivity measurements as well as ultraviolet-visible and infrared spectroscopy. In these complexes the selenite or tellurite ligand coordinates to platinum(II) or palladium(II) as bidentate with two oxygen atoms. These complexes inhibit the growth of P 388 lymphocytic leukemia cells, their targets are DNA. The selenite complexes invariably show I.D.50 values less than cisplatin. However, the I.D.50 values of the tellurite complexes are usually higher than cisplatin, except that of [Pd(dach)(TeO3)] which has comparable I.D.50 values, as compared to cisplatin. [Pt(bipy)(SeO3)] and [Pd(bipy)(SeO3)] have been interacted with calf thymus DNA and bind to DNA through a coordinate covalent bond.

Synthesis, spectroscopic, cytotoxic, and DNA binding studies of binuclear 2,2'-bipyridine-platinum(II) and -palladium(II) complexes of meso-alpha,alpha'-diaminoadipic and meso-alpha,alpha'-diaminosuberic acids.

Four new binuclear complexes of formula [M2(bipy)2(BAA)]Cl2 (where M is Pt(II) or Pd(II), bipy is 2,2'-bipyridine, and BAA is a dianion of meso-alpha-alpha'-diaminoadipic acid (DAA) or meso-alpha,alpha'-diaminosuberic acid (DSA) have been synthesized. These complexes have been characterized by chemical analysis and ultraviolet-visible, infrared, and 1H NMR spectroscopy. The mode of binding of ligands in these complexes has been ascertained by infrared and detailed 1H NMR spectroscopy. These complexes are 1:2 electrolyte in conductivity water. They have also been tested against P388 lymphocytic leukemia cells and their target is DNA molecules. [Pt2(bipy)2(DSA)]Cl2, [Pd2(bipy)2(DSA)Cl2, and [Pd2(bipy)2(DAA)]Cl2 show I.D.50 values comparable or lower than cis-diamminedichloroplatinum(II) and [Pt(bipy)(Ala)]Cl. In addition, binding studies of [Pt2(bipy)2(DSA)]Cl2 and [Pd2(bipy)2(DAA)]Cl2 to calf thymus DNA have been carried out and the mode of binding seems to be hydrogen bonding, as suggested earlier for analogous mononuclear amino acid-DNA complexes.