Synthesis, computational study, solvatochromism and biological studies of thiazole-owing hydrazone derivatives

In the present work, we have synthesized thiazole-hydrazone conjugates 5(a–h) and characterized them using various analytical techniques such as UV, IR, NMR, and mass spectrometry. Solvatochromic properties were evaluated in ten solvents with different polarity and quantum chemical parameters using a DFT study. The antibacterial activity results revealed that compounds 5c, 5d and 5g exhibited good efficacy and that the remaining compounds displayed significant activity. The synthesized compounds were screened for their cytotoxic activity against HepG2 and MCF-7 cell lines, and all the synthesized compounds exhibited significant potency towards the screened cancer cell lines. The anti-inflammatory efficacy of the synthesized thiazole derivatives was determined against MMP-2 and MMP-9, and some of the compounds showed significant activity. Furthermore, the in silico molecular docking was performed with the COX-2 receptor

Metal triflates catalyzed efficient synthesis of 3,4-dihydro-2H-1-benzopyrans

Ytterbium triflate efficiently catalyzes an unusual cyclization of o-hydroxybenzaldehydes with 2,3-dihydrofuran and 3,4-dihydro-2H-pyran in the presence of trimethyl orthoformate at ambient temperature to afford a new class of compounds, furo- and pyrano[2,3-b]benzopyrans in excellent yields with high diastereoselectivity. Also, o-hydroxybenzaldehydes reacted smoothly with acetophenones in the presence of a catalytic amount of scandium triflate under similar reaction conditions to give the corresponding 2,4-dialkoxy-2-aryl-3,4-dihydro-2H-1-benzopyrans in high yields

Challenges and opportunities in mixed method data collection on mental health issues of health care workers during COVID-19 pandemic in India

Background: The present paper describes the key challenges and opportunities of mixed method telephonic data collection for mental health research using field notes and the experiences of the investigators in a multicenter study in ten sites of India. The study was conducted in public and private hospitals to understand the mental health status, social stigma and coping strategies of different healthcare personnel during the COVID-19 pandemic in India.Methods: Qualitative and quantitative interviews were conducted telephonically. The experiences of data collection were noted as a field notes/diary by the data collectors and principal investigators.Results: The interviewers reported challenges such as network issues, lack of transfer of visual cues and sensitive content of data. Although the telephonic interviews present various challenges in mixed method data collection, it can be used as an alternative to face-to-face data collection using available technology.Conclusions: It is important that the investigators are well trained keeping these challenges in mind so that their capacity is built to deal with these challenges and good quality data is obtained

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

InCl<SUB>3</SUB>-catalyzed stereoselective synthesis of C-glycosyl heteroaromatics

Glycals react smoothly with furan in the presence of a catalytic amount of indium trichloride at ambient temperature to afford predominantly the C-3-substituted glycals in high yields. Other heteroaromatics including 2-benzyloxymethylfuran, thiophene and N-Boc protected indole afford exclusively C-1-glycosides in good yields with high β-selectivity under similar reaction conditions

InCl<SUB>3</SUB>-catalyzed hetero-Diels-Alder reaction: an expeditious synthesis of pyranoquinolines

Indium trichloride catalyzes efficiently the cycloaddition reactions of aryl amines with 3,4-dihydro-2H-pyran (DHP) under mild reaction conditions to afford the corresponding pyrano[3,2-c]quinolines in high yields with high diastereoselectivity

LiBF<SUB>4</SUB>-catalyzed formation of fused pyrano- and furanobenzopyrans

Lithium tetrafluoroborate efficiently catalyzes an unusual cyclization of o-hydroxybenzaldimines with 2,3-dihydrofuran and 3,4-dihydro-2H-pyran at ambient temperature to afford a class of new pyrano- and furanobenzopyran derivatives in excellent yields with high diastereoselectivity

Rapid and efficient synthesis of optically active pyrazoles under solvent-free conditions

2-Formyl glycals undergo rapid condensation with arylhydrazines under solvent-free conditions to give the corresponding optically pure 4-substituted pyrazoles in good yields with high selectivity. The stereochemistry of the products was assigned by various NMR experiments

Iodotrimethylsilane induced diastereoselective synthesis of tetrahydropyranones by a tandem Knoevenagel-Michael reaction

The synthesis of multifunctionalized tetrahydropyranones has been achieved at room temperature with iodotrimethylsilane by a tandem Knoevenagel condensation of aldehydes with aldol adducts prepared from β-keto esters and aldehydes, followed by a Michael reaction. The reactions are highly diastereoselective affording a single isomer in high yields