Epithelial-to-mesenchymal transition based diagnostic and prognostic signature markers in non-muscle invasive and muscle invasive bladder cancer patients.

BACKGROUND: Diagnostic and prognostic significance of epithelial-to-mesenchymal transition (EMT) associated biomarkers are evaluated in a cohort of NMIBC (non-muscle invasive bladder cancer) and MIBC (muscle invasive bladder cancer) patients. METHODS AND RESULTS: Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining were carried out in 100 tumor specimens (59 NMIBC and 41 MIBC). The expressions of the epithelial marker, mesenchymal markers and EMT-activating transcription factors (EMT-ATFs) were determined at transcriptome and protein level followed by their statistical associations with clinicohistopathological variables of the patients. Transcriptomic expression analysis showed statistical relevance of tumor stage with increased Twist and Zeb-1; tumor type with reduced E-cadherin and increased Snail; and smoking/tobacco chewing status (S/TC) of patients with increased N-cadherin and Snail in NMIBC patients. Tumor grade with reduced message E-cadherin, gain of N-cadherin, Snail, Twist and Zeb-1; patients' age with reduced E-cadherin and Twist gain; and tumor type with increased message N-cadherin exhibited associations in MIBC patients. Protein expression analysis identified statistical relevance of tumor grade with nuclear gain of Snail and Twist; and nuclear gain of Slug with S/TC status of NMIBC patients. Novel gain of membranous Vimentin deduced association with patients' age in MIBC patients. Survival analysis identified novel Vimentin as the positive predictor of short progression free survival (PFS) and short overall survival (OS) in MIBC patients. Study established altered EMT profile as the independent negative predictor of short recurrence free survival (RFS) in NMIBC patients and positive predictor of short PFS and OS in MIBC patients. CONCLUSIONS: EMT associated biomarkers could provide diagnostic and prognostic risk stratification and hence could be of importance in the clinical management of bladder cancer patients.

B4GAT1 Gene Associated Congenital Muscular Dystrophy Presenting with Recurrent Severe Ventriculomegaly: Case Report and Review of Literature.

BACKGROUND: Congenital muscular dystrophies (CMD) range in phenotype from an antenatal presentation with brain and eye anomalies to isolated muscular weakness. B4GAT1 gene has recently been associated with muscular dystrophy-dystroglycanopathy, type A, 13 and two families have been reported. CASE REPORT: We report the third family with B4GAT1 associated CMD presenting as recurrent severe ventriculomegaly, cerebellar and vermian hypoplasia in fetal life, which was identified after the second affected pregnancy. The mutations identified were similar to those reported in a previously reported Indian family, homozygous, p.Asn390Asp, and p. Ala406Val, suggesting founder mutation. CONCLUSION: B4GAT1 mutations are associated with CMD and may present in fetal life as severe ventriculomegaly. The homozygous B4GAT1 mutations, p.Asn390Asp, and p. Ala406Val, described in two Indian families (including this case) might represent a founder mutation.

Role of MCP-1 on inflammatory processes and metabolic dysfunction following high-fat feedings in the FVB/N strain.

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is known to be an important chemokine for macrophage recruitment. Thus, targeting MCP-1 may prevent the perturbations associated with macrophage-induced inflammation in adipose tissue. However, inconsistencies in the available animal literature have questioned the role of this chemokine in this process. The purpose of this study was to examine the role of MCP-1 on obesity-related pathologies. METHODS: Wild-type and MCP-1-deficient mice on an friend virus B NIH (FVB/N) background were assigned to either low-fat diet or high-fat diet (HFD) treatment for a period of 16 weeks. Body weight and body composition were measured weekly and monthly, respectively. Fasting blood glucose and insulin, and glucose tolerance were measured at 16 weeks. Macrophages, T-cell markers, inflammatory mediators and markers of fibrosis were examined in the adipose tissue at the time of killing the mice. RESULTS: As expected, HFD increased adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysfunction (impaired glucose metabolism and insulin resistance) macrophage number (CD11b(+)F480(+) cells, and gene expression of EMR1 and CD11c), T-cell markers (gene expression of CD4 and CD8), inflammatory mediators (pNFκB and pJNK, and mRNA expression of MCP-1, CCL5, C-X-C motif chemokine-14, tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6)) and fibrosis (expression of IL-10, IL-13, TGF-ß and matrix metalloproteinase-2 (MMP2); P<0.05). However, contrary to our hypothesis, MCP-1 deficiency exacerbated many of these responses resulting in a further increase in adiposity (body weight, fat mass, fat percent and adipocyte size), metabolic dysregulation, macrophage markers (EMR1), inflammatory cell infiltration and fibrosis (formation of type I and III collagens, mRNA expression of IL-10 and MMP2; P<0.05). CONCLUSIONS: These data suggest that MCP-1 may be a necessary component of the inflammatory response required for adipose tissue protection, remodeling and healthy expansion in the FVB/N strain in response to HFD feedings.

Comparative study of seasonal variation in bacterial flora concomitant with farm raised fingerlings of Cyprinus carpio at tarai region of Uttarakhand.

The bacterial infection is an important economic and limiting factor in intensive fish production. The present study focuses on investigation of the bacterial population associated with farmed common carp fingerlings, its environment and limnological quality of pond, during winter and summer season. It was found that the bacterial count in the pond sediment (6.40 cfu x 10(4)) was about 10 times higher in comparison of pond water (6.93 cfu x 10(3)). Further, the intestinal bacterial count was about 100 times higher (6.67 cfu x 10(5)) during winter and 1000 times higher (2.33 cfu x 10(6)) during summer season in comparison to the surfacial skin of fish during winter and summer (3.39 and 8.87 cfu x 10(3)), respectively. The isolated bacteria were both Gram negative and Gram positive, mostly aerobic rods. Furthermore, the temperature showed a significant relation with the bacterial counts of pond water. In the summer season, higher bacterial counts (8.72 cfu x 10(3)) were recorded as compared to winter (5.13 cfu x 10(3)). The dominant bacteria isolated from the sample of pond water, pond sediment and fish were identified as Aeromonas hydrophila, Pseudomonas fluorescens, Pseudomonas sp., Flavobacter sp., Bacillus sp., Micrococcus sp., Corynebacterium sp. Moreover, the bacterial density was dependent on C:N values, and the optimum range of C: N ratio was found between 16-23, for the carp culture ponds. Among the isolated bacterial flora, the presence of strains which were well known for their probiotic properties suggested an autochthonous source for use in aquaculture. Further, analysis of various physico-chemical parameters of pond water revealed that they were within the suitable range for the freshwater fish culture throughout farming phase.

Morphological traits association with fodder and seed yield in Vigna unguiculata (L.).

In cowpea, dual purpose plant types are more preferable for cultivation. Therefore, exotic and indigenous cowpea germplasm lines were evaluated in augmented design to study estimates of the correlation coefficients and path analysis of morphological as well as fodder and grain yield attributes. The present study showed a high impact of direct effects of correlation (0.9714**) and suggested that going for plant types with higher biomass per plant (0.8856**), dry weight per plant (0.4598), stem girth (0.2336) number of secondary branches (0.2788), leaves per plant (0.3251), pods per plant (0.9059) and pod clusters per plant (0.7718) would be effective for improving both fodder and seed yield in cowpea.

In vitro antimalarial activity and molecular docking analysis of 4-aminoquinoline-clubbed 1,3,5-triazine derivatives.

AIMS: Present report describes the in vitro antimalarial activity and docking analysis of seven 4-aminoquinoline-clubbed 1,3,5-triazine derivatives on pf-DHFR-TS. METHODS AND RESULTS: The antimalarial activity was evaluated in vitro against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compounds were docked onto the active site of pf-DHFR-TS using docking server to explicate necessary structural requirements for antimalarial activity. CONCLUSION: Title molecules demonstrated considerable bioactivity against the malaria parasite. Docking analysis revealed deep engulfment of the molecules into the inner groove of pf-DHFR-TS active site by making stable ligand-receptor posses. Hydrophobic interaction was identified as the only major interacting force playing a role between ligand-receptor interaction and minor with hydrogen bonds. SIGNIfiCANCE AND IMPACT OF THE STUDY: The study provided the novel insight into the necessary structural requirement for rationale-based antimalarial drug discovery.

The impact of fluence dependent 120 MeV Ag swift heavy ion irradiation on the changes in structural, electronic, and optical properties of AgInSe2 nano-crystalline thin films for optoelectronic applications.

Swift heavy ion (SHI) irradiation in thin films significantly modifies the structure and related properties in a controlled manner. In the present study, the 120 MeV Ag ion irradiation on AgInSe2 nanoparticle thin films prepared by the thermal evaporation method and the induced modifications in the structure and other properties are being discussed. The ion irradiation led to the suppression of GIXRD and Raman peaks with increasing ion fluence, which indicated amorphization of the AgInSe2 structure along the path of 120 MeV Ag ions. The Poisson's fitting of the ion fluence dependence of the normalized area under the GIXRD peak of AgInSe2 gave the radius of the ion track as 5.8 nm. Microstructural analysis using FESEM revealed a broad bi-modal distribution of particles with mean particle sizes of 67.5 nm and 159 nm in the pristine film. The ion irradiation led to the development of uniform particles on the film surface with a mean size of 36 nm at high ion fluences. The composition of the film was checked by the energy dispersive X-ray fluorescence (EDXRF) spectrometer. The UV-visible spectroscopy revealed the increase of the electronic bandgap of AgInSe2 films with an increase in ion fluence due to quantum confinement. The Hall measurement and EDXRF studies showed that the unirradiated and irradiated AgInSe2 films have n-type conductivity and vary with the ion fluence. The changes in the films were tuned with different ion fluence and are favorable for both optical and electronic applications.

Cu(I) complexes obtained via spontaneous reduction of Cu(II) complexes supported by designed bidentate ligands: bioinspired Cu(I) based catalysts for aromatic hydroxylation.

Copper(i) complexes [Cu(L1-7)2](ClO4) (1-7) of bidentate ligands (L1-L7) have been synthesized via spontaneous reduction and characterized as catalysts for aromatic C-H activation using H2O2 as the oxidant. The single crystal X-ray structure of 1 exhibited a distorted tetrahedral geometry. All the copper(i) complexes catalyzed direct hydroxylation of benzene to form phenol with good selectivity up to 98%. The determined kinetic isotope effect (KIE) values, 1.69-1.71, support the involvement of a radical type mechanism. The isotope-labeling experiments using H218O2 showed 92% incorporation of 18O into phenol and confirm that H2O2 is the key oxygen supplier. Overall, the catalytic efficiencies of the complexes are strongly influenced by the electronic and steric factor of the ligand, which is fine-tuned by the ligand architecture. The benzene hydroxylation reaction possibly proceeded via a radical mechanism, which was confirmed by the addition of radical scavengers (TEMPO) to the catalytic reaction that showed a reduction in phenol formation.

Outcomes of Primary Arteriovenous Fistula for Hemodialysis in Elderly Patients (>65 Years) with End Stage Renal Disease: A Study on Indian Population.

INTRODUCTION: The outcome of arteriovenous fistula (AVF) for hemodialysis (HD) in elderly population remains an issue. The aim of our study was to evaluate the outcomes of arteriovenous fistulas created at our institute in patients older than 65 years. METHODS: All chronic HD patients with age >65 years who had an AVF created between January 1, 2010 and January 1, 2017 were included retrospectively. Baseline demographic information including age, gender, etiology of renal failure and comorbidities were recorded. Access characteristics including access type and anatomic location were recorded. The end point of study was primary and secondary patency. Minimum follow up period of study was 1 year. RESULTS: A total of 422 AVF were created within the study period. The mean age was 69.3 years. The anatomical site of AVF creation was radiocephalic (RCF) in 74.8% (n = 316), brachiocephalic (BCF) in 18.9% (n = 80) and brachiobasilic (BBF) in 6.1% (n = 26). At one year after creation, cumulative survival of the AVF was 64.7%. At 36 months the primary and secondary patency of RCF, BCF and BBF was 43.6%, 58.6%, 42.6% and 47.3%, 62.5%, 56.9% respectively. The overall median survival did not differ between RCF and BBF fistulas. However, when both were compared with BCF (median survival 1034 days), BBF (median survival 741 days) and RCF (median survival 592 days) had significantly poorer survival (P = 0.004). The most common reason for access failure was thrombosis (28.4%) followed by failure to mature (9%) and aneurysm related complications (9%). CONCLUSIONS: Age should not be a limiting factor when choosing AVF as the preferred HD access. Brachiocephalic AVF has better primary and secondary patency with higher overall median survival. However RCF also provides reasonably good survival rates with acceptable complications in elderly population. Thrombosis and fistulas that fail to mature present as a primary concern to patients in elderly population, and demand further study.

Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.

Although it has been demonstrated that transformed progenitor cell population can contribute to tumor initiation, factors contributing to this malignant transformation are poorly known. Using in vitro and xenograft-based models, previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by targeting various oncogenic pathways. It has been demonstrated that miR-489 directly targets HER2 and inhibits the HER2 signaling pathway; however, its role in mammary gland development and HER2-induced tumor initiation hasn't been studied. To dissect the role of miR-489, we sorted different populations of mammary epithelial cells and determined that miR-489 was highly expressed in mammary stem cells. MMTV-miR-489 mice that overexpressed miR-489 in mammary epithelial cells were developed and these mice exhibited an inhibition of mammary gland development in early ages with a specific impact on highly proliferative cells. Double transgenic MMTV-Her2-miR489 mice were then generated to observe how miR-489 overexpression affects HER2-induced tumorigenesis. miR-489 overexpression delayed HER2-induced tumor initiation significantly. Moreover, miR-489 overexpression inhibited tumor growth and lung metastasis. miR-489 overexpression reduced mammary progenitor cell population significantly in preneoplastic mammary glands of MMTV-Her2 mice which showed a putative transformed population in HER2-induced tumorigenesis. The miR-489 overexpression reduced CD49fhiCD61hi populations in tumors that have stem-like properties, and miR-489 overexpression altered the HER2 signaling pathway in mammary tumors. Altogether, these data indicate that the inhibition of HER2-induced tumorigenesis by miR-489 overexpression was due to altering progenitor cell populations while decreasing tumor growth and metastasis via influencing tumor promoting genes DEK and SHP2.

Correction: Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.

In the published version of this paper the author A. Awgulewitsch's surname was incorrectly given as Awagulerwitsch instead of Awgulewitsch. This has now been corrected in the HTML version of the paper, the PDF was correct at the time of publication.

Changes in serum leptin, insulin, androstenedione and luteinizing hormone during ovarian cycle in the bat, Taphozous longimanus.

Detailed reproductive pattern and associated endocrine characteristics have been documented in only a few species of order Chiroptera. The aim of the present study was to examine the changes in body weight, serum insulin, leptin, androstenedione and luteinizing hormone (LH) concentrations during annual ovarian cycle in the sheath-tailed bat, Taphozous longimanus. Bats were sampled over three years. Leptin, a satiety hormone produced primarily by adipose tissue, provides information to feeding center of the brain about nutritional status, fat mass, appetite and energy expenditure. The circulating concentration of leptin begins to increase from October and attains a peak in December. The peak serum leptin concentration coincides with body weight in November before winter dormancy in December. The serum leptin levels dissociate from body weight during December. The other peaks of serum leptin levels coincide with late stages of the two successive pregnancies. The serum insulin concentration begins to increase from September and attains a peak during December. The insulin concentration remains low from January to August. The circulating androstenedione concentration begins to increase in October, reaching a peak in December. This increase in androstenedione concentration correlated with the period of heavy accumulation of abdominal fat and increase in body weight. There was a sharp decline in androstenedione concentration and body weight in January. The serum LH shows peaks, in November, coinciding with the peaked body weight, the other peaks in January and May, coinciding with ovulation for the two successive pregnancies. The high leptin and insulin levels might be responsible for the maintenance of reproductive response and gonadal function during adverse environmental condition in the winter, while high androstenedione, and associated body weight along with LH might be responsible for maintaining basal gonadal function. We conclude that high leptin, androstenedione and insulin serve, as signal for the reproductive functions in that sufficient body fat are available to meet the caloric demands and maintain normal function during adverse winter conditions.

Combined experimental and theoretical studies on selective sensing of zinc and pyrophosphate ions by rational design of compartmental chemosensor probe: Dual sensing behaviour via secondary recognition approach and cell imaging studies.

A compartmental chemosensor probe HL has been designed and synthesized for the selective recognition of zinc ions over other transition metal ions via fluorescence "ON" strategy. The chemosensing behaviour of HL was demonstrated through fluorescence, absorption and NMR spectroscopic techniques. The molecular structure of the zinc complex derived from HL was determined by X-ray crystallography. A probable mechanism of this selective sensing behavior was described on the basis of spectroscopic results and theoretical studies by density functional theory (DFT). The biological applicability of the chemosensor HL was examined via cell imaging on HeLa cells. The HL-zinc complex served as a secondary fluorescent probe responding to the pyrophosphate anion specifically over other anions. The fluorescence enhancement of HL in association with Zn2+ ions was quenched in the presence of pyrophosphate (PPi). Thus, a dual response was established based on "OFF-ON-OFF" strategy for detection of both cation and anion. This phenomenon was utilized in the construction of a "INHIBIT" logic gate.

A highly selective chromogenic sensor for Mn2+, turn-off fluorometric for Hg2+ ion, and turn-on fluorogenic sensor for F- ion with the practical application.

A colorimetric and fluorometric probe (E)-2-((8-hydroxy-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-yl)methylene)hydrazinecarbothioamide based on thiosemicarbazide and julolidine moieties has been synthesised in pure crystalline form and characterized by 1H NMR, UV-vis, elemental analysis and single crystal XRD. The probe functioned as multitarget ion sensor, detect biologically important metal ions Hg2+ and Mn2+ in dual channel mode. Meanwhile, in mixed solvent media DMF/H2O [8:2], probe displayed selectivity for Hg2+ over other cations by the emission spectrum. Interestingly probe has been explored to recognize F- anion in DMF through ESIPT mechanism. The 1:1 binding stoichiometry of probe with Hg2+ and Mn2+ is confirmed by Job's plot through emission titration and UV-vis titration respectively. Probe is selective and sensitive to Hg2+ and Mn2+ with detection limit as low as 15µM and 0.2µM respectively. The sensing mechanism for selective ions was also scrutinized using 1H NMR experiments and computational studies.

Differential methods of inoculation of plant growth-promoting rhizobacteria induce synthesis of phenylalanine ammonia-lyase and phenolic compounds differentially in chickpea.

Foliar spray and micro-injection of plant growth-promoting rhizobacterial species, viz. Pseudomonas fluorescens and P. aeruginosa on chickpea induced synthesis of phenylalanine ammonia-lyase (PAL) when tested against Sclerotinia sclerotiorum. Induction of PAL was also associated with increased synthesis of phenolic compounds such as tannic, gallic, caffeic, chlorogenic and cinnamic acids. Treatment with P. fluorescens was found to be more effective in inducing phenolic compounds as compared to P. aeruginosa. However, persistence of PAL activity was observed more with P. aeruginosa. Although both the inoculation methods were effective, foliar application was found to be superior to micro-injection in terms of rapid PAL activity leading to the synthesis of phenolic compounds.

Functional and structural comparison of nitric oxide reductases from denitrifying fungi Cylindrocarpon tonkinense and Fusarium oxysporum.

Two isozymes of nitric oxide reductase (Nor) from the denitrifying fungus Cylindrocarpon tonkinense (c.Nor1 and c.Nor2) are the heme-enzyme cytochrome P-450's (Usuda et al. (1995) Appl. Environ. Microbiol. 61, 883-889). However, they catalyze the NO reduction to N2O, but not the monooxygenation reaction using O2. We kinetically and spectrophotometrically studied the reactions of the two Nor's with NO and electron donor, NAD(P)H, using flash-photolysis and stopped-flow rapid scan methods. The enzyme in the Fe3+ state can bind NO to yield the Fe3+ NO complex. When the resultant Fe3+ NO complex reacted with the electron donor, it was converted to the Fe3+ enzyme via a transient formation of the characteristic intermediate (I). The spectroscopic results were essentially the same as those of the Nor from another denitrifying fungus Fusarium oxysporum (f.Nor), which we previously reported (Shiro et al. (1995) J. Biol. Chem. 270, 1617-1623), suggesting that these fungal Nor's catalyze the NO reduction by the same mechanism. Most probably, the Fe3+ NO complex of the Nor is reduced with two-electrons directly transferred from NAD(P)H to yield the intermediate I, and then the I reacts with another NO to generate N2O and the Fe3+ enzyme. However, the kinetic measurements showed that the reaction rate constant of each step was variable depending on the combination of the Nor and the electron donor; i.e., c.Nor1 + NADH, c.Nor2 + NADPH, c.Nor2 + NADH and f.Nor + NADH. In particular, the rate constant for the electron transfer step from the electron donor to the Fe3+ NO enzyme is dramatically different among these systems. On the other hand, we also measured paramagnetically shifted 1H-NMR spectra of c.Nor2 and f.Nor in the ferrous (reduced) state, where the iron-bound Cys beta-CH2 signal was observed at the same position (approximately 270 ppm) for c.Nor2 and f.Nor, indicating that the Cys thiolate (S-) coordinates to the heme iron in the same fashion in the Nor's. However, the heme peripheral proton signals were subtly but significantly different in their positions between the two enzymes. On the basis of these kinetic and spectroscopic data, we suggested that the Fe-S- binding character is not essential for the NO reduction reactivity, but that the subtle difference in interaction of their hemes with the surroundings is possibly responsible for the difference in the Nor reactivity, especially in the electron transfer step from NAD(P)H to the Fe3+ NO moiety.

The effects of heme modification on reactivity, ligand binding properties and iron-coordination structures of cytochrome P450nor.

Artificial cytochrome P450nors (nitric oxide reductase) were prepared by replacing the native protoheme with various 2,4-substituted hemes: meso-, deutero-, and diacetyldeutero-hemes. For these samples, the ratio of low spin/high spin states of the ferric resting enzyme were varied, indicating that the coordination of the water molecule at the iron sixth site was affected by the electron withdrawing capacities of the heme 2,4-substituents. The binding of the water molecule reduces the rate of binding of nitric oxide (NO) to the ferric iron. In addition, the reduction reaction of the ferric-NO complex with NADH, which constitutes the second step in the NO reduction, was facilitated by the electron withdrawing capacity of 2,4-substituents. Consequently, proto- (native-) P450nor exhibited the highest overall enzymatic activity (NO reduction activity), while the enzymes containing diacetyl-, deutero-, and meso-hemes had considerably lower activities, since the NO reduction activity is determined by a balance of the reaction rates of the above two steps. The optical absorption spectra of the ferric-NO and the ferrous-CO complexes of the reconstituted enzymes show that the electron density on the heme in both states was modulated by the substituent groups. However, the resonance Raman spectral measurements showed that the Fe-NO and N-O stretching frequencies in the ferric-NO complex were insensitive to the electron density of the heme while the Fe-CO and C-O stretching frequencies in the ferrous-CO complex were sensitively varied by the electron withdrawing capacity of the 2,4-substituent. The differences are discussed in terms of the difference in the iron-ligand bond characters between the ferric-NO and the ferrous-CO complexes.

Histochemical localization of enzymes and lipids in the ovary of a vespertilionid bat, Scotophilus heathi, during the reproductive cycle.

The present study describes seasonal changes in delta5 3beta hydroxysteroid dehydrogenase (3beta-HSD), glusose-6 phosphates dehydrogenase (G-6-PD), and lipids in the ovary of a vespertilionid bat, Scotophilus heathi. Total lipids and 3beta-HSD activity are restricted to thecal and interstitial cells of the ovary. The total lipids, 3beta-HSD, and G-6-PD significantly increase during recrudescence, and remain high during winter dormancy and breeding as compared to the other reproductive phases. High incidence of lipids and enzyme activity in interstitial cells during the breeding period and at the time of ovulation clearly suggests that these cells are actively involved in steroidogenesis. A decline in enzymes and lipid activity during winter dormancy, which correlates with the declining levels of steroidogenesis, might be the factors responsible for prolonged survival of the Graafian follicle in the ovary of S. heathi.

Synthesis, characterization, and antitumor activity of 5-iodouracil complexes.

Complexes of 5-iodouracil (5IU) with Mn(II), Co(II), Cu(II), Zn(II), and Cd(II) ions have been prepared, characterized, and subjected to a screening system for evaluation of antitumor activity against Sarcoma-180 (S-180) and L 929 tumor cells. The complexes were characterized by their elemental analysis, infrared spectra, electronic spectra, magnetic measurements, and powder x-ray diffraction. The antitumor activity results indicate that some complexes have good antitumor activity both in vivo and in vitro against S-180 and L 929 tumor cells.

The effect of histidine on the structure and antitumor activity of metal-5-halouracil complexes.

The ternary complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) ions with 5-halouracils, viz., 5-fluorouracil (5FU), 5-chlorouracil (5ClU), and 5-bromouracil (5BrU), and the biologically important ligand L-histidine (HISD) have been synthesized and characterized by elemental analysis, conductance measurements, infrared spectra, electronic spectra, and magnetic moment (room temperature) measurements. On the basis of these studies, the structures of the complexes have been proposed. All these ternary complexes were screened for their antitumor activity against Dalton's lymphoma in C3H/He mice. It was found that only Mn(II)-5BrU-HISD, Co(II)-5BrU-HISD, Cu(II)-5ClU-HISD, Cu(II)-5BrU-HISD, Zn(II)-5FU-HISD, and Zn(II)-5BrU-HISD complexes have significant antitumor activity with T/C greater than 125% (where T and C represent mean lifespan of treated mice and control mice respectively). The Mn(II)-5FU-HISD, Co(II)-5FU-HISD, Co(II)-5ClU-HISD, Ni(II)-5ClU-HISD, Ni(II)-5BrU-HISD, and Zn(II)-5ClU-HISD complexes are also effective antitumor agents, with T/C greater than 115%. The complexes that showed effective antitumor action in vivo were also found to inhibit 3H-thymidine incorporation (DNA replication) in Dalton's lymphoma cells in vitro.