Synthesis of 1-β-D-Ribofuranosyl-5-ethoxycarbonyl-4- hydroxy -l,2-dihydropyrid-2-one

I-β-D-Ribofuranosyl-5-ethoxycarbonyl-4-hydroxy-1,2-dihydropyrid-2-one has been synthesized starting from 2,4-dihydroxy-5-ethoxycarbonylpyridine. The monomercury derivative of the starting compound on condensation with 2,3,5-tri-O-benzoylribofuranosyl chloride affords benzoylated nucleoside which on debenzoylation in the presence of catalytic amount of sodium methoxide in the methanol furnishes the desired nucleoside

A new synthesis of 4-hydroxycoumarins

4-Hydroxynaphthocoumarin has been synthesised by the internal condensation ofO-carbethoxy-2-acetyl-1-naphthol, thus suggesting a new general method for the synthesis of 4-hydroxycoumarins. The behaviour of 4-hydroxynaphthocoumarin has been studied; its derivatives including the corresponding dicoumarin have been prepared. By the action of potassium carbonate or sodamide on the carbethoxy ester of 2-acetyl-1-naphthol, a second product was obtained, the constitution of which is under examination

Synthetical experiments in the chromone group part XXI. synthesis of gentisin, the colouring matter of gentian root

This article does not have an abstract

A new synthetic approach to 8-aza analogs of prostaglandins

A new synthetic approach to (dl)-8-aza-13,14-dihydroprostanoic acid and its corresponding ll-hydroxy derivative is described

Protection of mice against Plasmodium berghei infection by a tuftsin derivative

In Plasmodium berghei infections, the mortality rate and parasitaemias were significantly reduced and the mean survival time was considerably enhanced by pretreating the animals with a tuftsin derivative, Thr-Lys-Pro-Arg-NH-(CH2)2-NHCOC15H31. This effect of the modified tuftsin was further increased upon its incorporation in the liposome bilayer. These results indicate that tuftsin and its derivatives may prove useful in enhancing nonspecific host resistance against protozoan infections

Synthesis of some potential antimycobacterial agents

This article does not have an abstract

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Art in organic synthesis

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A possible basis for structure function relationship of estrogens

It is well known that a wide variety of molecules compete for binding to the estrogen receptor and act as estrogens and/or antiestrogens. These molecules such as estradiol, diethylstilbestrol, doisynolic acid, the triarylethylenes, and cyclofenyl apparently share little resemblance which could account for their interaction with a common estrogen binding site. Knowledge of the receptor binding of triarylethylene and cyclofenyl prototypes, in particular, relative to that of the other estrogens is critical for understanding their structure-function relationship. We have carried out a study on the receptor binding specificity of triarylethylene and cyclofenyl prototypes. This study has revealed that these molecular types share considerable resemblance in their receptor binding specificity and differ from estradiol and other similar molecules in some important respects. However, comparison of their substructural binding specificities reveals the possibility that the triarylethylene and estradiol prototypes may interact with at least some common regions of the estrogen binding site. Based on this reasoning the comparative receptor binding of estrogens has been rationalized on the basis of a subsite hypothesis for the estrogen binding site. According to this hypothesis, the composite estrogen binding site is composed of essentially five subsites, and that the structurally different estrogenic prototypes can interact with different set of subsites, and thus differ in their binding orientation. The essential difference in the activity profile of estradiol prototypes and the triarylethylene antiestrogens reveals the possibility of a causal relationship between the binding orientation of a ligand and its activity profile. This model for receptor site can thus serve as a working hypothesis to rationalize the structure-function relationship of estrogens