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Research reveals that the Munavalli methodology for the synthesis of azacyanine is applicable to a wide variety of compounds and leads to the formation of heterocycles that are otherwise difficult to prepare. The synthetic route is a one-step reaction involving amino-substituted heterocycles reacting with diiodomethane to form azacyanines.

Abstract Background The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response to ABVD chemotherapy regimen. Methods a total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism. Results these studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05). Conclusions these results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.

A one-step heterocyclization of o-nitrobenzylamines to 3-alkoxy-2H-indazoles is reported. The electronic nature of the nitrophenyl group, the steric and electronic nature of R(super 1)-functionalized benzylic amine, and the nature of the alcoholic solvent affect the efficiency of this heterocyclization reaction (~40-90%).

Abstract Introduction We have shown that the radio sensitizer DCQ enhances sensitivity of HCT116 human colon cancer cells to hypoxia. However, it is not known whether the p53 or p21 genes influence cellular response to DCQ. In this study, we used HCT116 that are either wildtype for p53 and p21, null for p53 or null for p21 to understand the role of these genes in DCQ toxicity. Methods HCT116 cells were exposed to DCQ and incubated under normoxia or hypoxia and the viability, colony forming ability, DNA damage and apoptotic responses of these cells was determined, in addition to the modulation of HIF-1α and of p53, p21, caspase-2, and of the ataxia telangiectasia mutated (ATM) target PIDD-C. Results DCQ decreased colony forming ability and viability of all HCT116 cells to a greater extent under hypoxia than normoxia and the p21-/-cell line was most sensitive. Cells had different HIF-1α responses to hypoxia and/or drug treatment. In p53+/+, DCQ significantly inhibited the hypoxia-induced increases in HIF-1α protein, in contrast to the absence of a significant HIF-1α increase or modulation by DCQ in p21-/- cells. In p53-/- cells, 10 μM DCQ significantly reduced HIF-1α expression, especially under hypoxia, despite the constitutive expression of this protein in control cells. Higher DCQ doses induced PreG1-phase increase and apoptosis, however, lower doses caused mitotic catastrophe. In p53+/+ cells, apoptosis correlated with the increased expression of the pro-apoptotic caspase-2 and inhibition of the pro-survival protein PIDD-C. Exposure of p53+/+ cells to DCQ induced single strand breaks and triggered the activation of the nuclear kinase ATM by phosphorylation at Ser-1981 in all cell cycle phases. On the other hand, no drug toxicity to normal FHs74 Int human intestinal cell line was observed. Conclusions Collectively, our findings indicate that DCQ reduces the colony survival of HCT116 and induces apoptosis even in cells that are null for p53 or p21, which makes it a molecule of clinical significance, since many resistant colon tumors harbor mutations in p53.

Abstract Background DCQ (2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide), a synthetic quinoxaline 1,4-dioxide, enhances the cytotoxic effect of ionizing radiation (IR) in vivo and in vitro. We sought to clarify whether increased radiation-induced DNA damage, decreased rate of damage repair, and the generation of reactive oxygen species (ROS) contribute to DCQ enhancement of IR. Methods Murine mammary adenocarcinoma EMT-6 cells were treated with DCQ for 4 h before exposure to 10 Gy IR. Treated cells were monitored for modulations in cell cycle, induction of DNA damage, and generation of ROS. Results Combined DCQ and IR treatments (DCQ+IR) induced rapid cell-cycle arrests in EMT-6 cells, particularly in S and G2/M phases. Alkaline comet assays revealed high levels of DNA damage in cells after exposure to DCQ+IR, consistent with damage-induced arrest. Unlike IR-only and DCQ-only treated cells, the damage induced by combined DCQ+IR was repaired at a slower rate. Combined treatment, compared to separate DCQ and IR treatments, activated DNA-protein kinase and induced more p-ATM, supporting a role for double strand breaks (DSBs), which are more toxic and difficult to repair than single strand breaks (SSBs). Contributing factors to DCQ radiosensitization appear to be the induction of ROS and DSBs. Conclusion Collectively, our findings indicate that radiosensitization by DCQ is mediated by DNA damage and decreased repair and that ROS are at least partially responsible.

Intramolecular bis-heterocyclization reaction is used to synthesize 5H-indazolo-[3,2-b]benzo[d]-1,3-oxazine. The derivatives obtained by reacting with different substrates showed a wide range of biological activities.

A general route to novel isoxazole-substituted dihydrodiazocinones is achieved, which proceeds by the condensation of tetrazines with cyclobutanones in methanolic KOH at room temperature. These eight-membered ring diaza heterocycles exist in relatively few, low energy, conformationally accessible states and experience limited conformational flexibility and conformational analysis confirms the twist-boat-chair (TBC) conformation as the major contributor to the thermodynamic isomer.

A simple preparation of 3-oxy-substituted 2H-indazole, by an unrecognized method is reported. The method constitutes an easy method for constructing a N-N single bond.

Professor Uri Shamir has commented on the book 'Diplomacy on the Jordon' written by the author in its February 2002 issue (Vol 26:1). Shamir's remarks about the negotiations in the book are quite impressive.

Tetrazines, which are highly pi-deficient systems, have been utilized as dienophiles in inverse electron demand cycloadditions, including condensation reactions with enamines and enolates. In all these enolate reactions, the ketone or aldehyde contains at least two protons on the same alpha-carbon, which allows for the concomitant dehydration after condensation and extrusion of nitrogen.

Glypican-3 is an oncofetal protein found to be overexpressed in different types of tumours, such as hepatocellular carcinoma, malignant melanoma, squamous cell carcinoma of the lungs and testicular yolk sac tumour. Glypican-3 is currently emerging as a tumour marker and/or potential target for therapy of many cancers. However, there are limited studies looking for glypican-3 expression in neuroblastoma, with some evidence for loss of expression. Therefore, we sought to investigate glypican-3 expression in primary and metastatic neuroblastoma and to explore its potential as marker and/or target for development of new therapy for neuroblastoma. A total of 31 archived tissue specimens of neuroblastoma were subjected to immunohistochemical staining using a monoclonal antibody specific for glypican-3.Glypican-3 expression was compared with clinical and histological characteristics for each patient. Immunohistochemical analysis revealed for the first time overexpression of glypican-3 in 33% of neuroblastoma tumours. Its overexpression was surprisingly more predominant in metastatic tumours (71%) than in primary tumours. Glypican-3 expression was significantly correlated with disease clinical stages (P ≤ 0.05). It was more frequently expressed in the majority of stage 4s patients and connoted poor disease prognosis. On this basis, the biological functions and molecular mechanisms underlying the overexpression of glypican-3 in neuroblastoma warrant further investigations, especially the promising use of glypican-3 for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]