Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC₅₀<10⁻⁴ M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.     

Tuning of ferrimagnetic nature and hyperfine interaction of Ni2+ doped cobalt ferrite nanoparticles for power transformer applications

Ferrites may contain single domain particles which gets converted into super-paramagnetic state near critical size. To explore the existence of these characteristic feature of ferrites, we have performed magnetization(M-H loop) and Mössbauer spectroscopic studies of Ni²⁺ substitution effect in Co_1-xNi_xFe₂O₄ (where x?=?0, 0.25, 0.5, 0.75 and 1) nanoparticles were fabricated by solution combustion route using mixture of carbamide and glucose as fuels for the first time. As prepared samples exhibit spinel cubic structure with lattice parameters which decreases linearly with increase in Ni²⁺ concentration. The M-H loops reveals that saturation magnetization(M_s), coercive field(H_c) remanence magnetization(M_r) and magnetron number(η_B) decreases significantly with increasing Ni²⁺ substitution. The variation of saturation magnetization has been explained on the basis of Neel's molecular field theory. The coercive field(H_c) is found strongly dependent on the concentration of Ni²⁺ and decrease of coercivity suggests that the particles have single domain and exhibits superparamagnetic behavior. The Mössbauer spectroscopy shows two ferrimagnetically relaxed Zeeman sextets distribution at room temperature. The dependence of Mössbauer parameters such as isomer shift, quadru pole splitting, line width and hyperfine magnetic field on Ni²⁺ concentration have been discussed. Hence our results suggest that synthesized materials are potential candidate for power transformer application.     

Suitability,efficiency and microbiological safety of novel physical technologies for the processing of ready‐to‐eat meals,meats and pumpable products

Consumer studies and market reports show an increase in consumption of ready‐to‐eat (RTE) foods. Although conventional processing technologies can in most cases produce safe products, they can also lead to the degradation of nutritional compounds and negatively affect quality characteristics. Consumers strongly prefer food that is minimally processed with the maximum amount of health‐promoting substances. Novel processing technologies as pre‐ or post‐treatment decontamination methods or as substitutes of conventional technologies have the potential to produce foods that are safe, rich in nutrient content and with superior organoleptic properties. Combining novel with conventional processes can eliminate potential drawbacks of novel technologies. This review examines available scientific information and critically evaluates the suitability and efficiency of various novel thermal and nonthermal technologies in terms of microbial safety, quality as well as nutrient content on the production of RTE meals, meats and pumpable products.     

Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.