Cyclohexane-1,3-dione derivatives are considered as a key structural precursor for the synthesis of plethora of synthetically significant compounds such as 4H-chromenones, 2H-xanthenones, coumarins, ...enaminones, acridinedione, 1,4-dihydropyridine, different other heterocycles, and natural products. These compounds show the diverse range of biological activities that include herbicidal, pesticidal, anti-bacterial, anti-inflammatory, anti-tumor, analgesic, anti-convulsant, anti-viral, anti-plasmodial, anti-malarial, anti-allergic, anti-cancer, etc. This versatility in the chemistry of cyclohexan-1,3-dione and its derivatives is due to the presence of highly active methylene moiety and its active di-carbonyl groups. There are only few reviews in the literature published on the synthetic application of cyclohexane-1,3-diones, but not on the synthesis of cyclohexane-1,3-dione and its derivatives. Keeping the importance of cyclohexane-1,3-dione derivatives in view, we inspired to do a compilation of their synthetic methods from different precursors, which are mainly published in last two decades.
Indolent non-Hodgkin's lymphomas (iNHLs) are incurable with standard therapy and are poorly responsive to checkpoint blockade. Although lymphoma cells are efficiently killed by primed T cells, in ...vivo priming of anti-lymphoma T cells has been elusive. Here, we demonstrate that lymphoma cells can directly prime T cells, but in vivo immunity still requires cross-presentation. To address this, we developed an in situ vaccine (ISV), combining Flt3L, radiotherapy, and a TLR3 agonist, which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs). ISV induced anti-tumor CD8
T cell responses and systemic (abscopal) cancer remission in patients with advanced stage iNHL in an ongoing trial ( NCT01976585 ). Non-responding patients developed a population of PD1
CD8
T cells after ISV, and murine tumors became newly responsive to PD1 blockade, prompting a follow-up trial of the combined therapy. Our data substantiate that recruiting and activating intratumoral, cross-priming DCs is achievable and critical to anti-tumor T cell responses and PD1-blockade efficacy.
Antiviral treatment of COVID-19 Şimşek Yavuz, Serap; Ünal, Serhat
Turkish journal of medical sciences,
04/2020, Letnik:
50, Številka:
SI-1
Journal Article
Recenzirano
Odprti dostop
Currently, there is not any specific effective antiviral treatment for COVID-19. Although most of the COVID-19 patients have mild or moderate courses, up to 5%–10% can have severe, potentially life ...threatening course, there is an urgent need for effective drugs. Optimized supportive care remains the mainstay of therapy. There have been more than 300 clinical trials going on, various antiviral and immunomodulating agents are in various stages of evaluation for COVID-19 in those trials and some of them will be published in the next couple of months. Despite the urgent need to find an effective antiviral treatment for COVID-19 through randomized controlled studies, certain agents are being used all over the world based on either in-vitro or extrapolated evidence or observational studies. The most frequently used agents both in Turkey and all over the world including chloroquine, hydroxychloroquine, lopinavir/ritonavir, favipiravir and remdesivir will be reviewed here .Nitazoxanide and ivermectin were also included in this review as they have recently been reported to have an activity against SARS-CoV-2 in vitro and are licensed for the treatment of some other human infections.
A new fourth-order difference approximation is derived for the space fractional derivatives by using the weighted average of the shifted Grünwald formulae combining the compact technique. The ...properties of proposed fractional difference quotient operator are presented and proved. Then the new approximation formula is applied to solve the space fractional diffusion equations. By the energy method, the proposed quasi-compact difference scheme is proved to be unconditionally stable and convergent in L2 norm for both 1D and 2D cases. Several numerical examples are given to confirm the theoretical results.
We have innovatively designed and assessed the hydrogen storage properties of a single Ti-doped C20 nanocage and its B, N or B and N heteroatom substituted derivatives with the help of the density ...functional theory approach for the first time to the best of our knowledge. Out of fifteen designed structures by substituting heteroatoms, only 8 structures are found to be suitable for Ti doping and H2 adsorption viz. C20, C12N8, C12B8, C12B4N4, C10B5N5, C10B10, B10C10 and B10N10. Their formation energy and cohesive energy values confirm the stability of all the structures. Ti atom binds more strongly with B, N or B and N heteroatom substituted C20 nanocage than unsubstituted C20 nanocage which is necessary to avoid clustering for multiple Ti doped nanocages. Among the eight Ti doped nanocages considered, H2 molecules strongly interact with Ti-doped C12B4N4 nanocage. The binding strength of Ti atom with nanocages decreases during the hydrogen adsorption process. The obtained H2 adsorption energy values for all the structures are within the range of 0.2–0.7 eV, which is conducive to reversible hydrogen storage. Calculated Gibbs free energy-corrected H2 adsorption energy values at different temperature and pressure indicate favorable H2 adsorption over the entire pressure range at room temperature. For Ti doped C20, C12N8, C12B8, C10B5N5, C10B10, B10N10, and B10C10 nanocages, H2 adsorption is thermodynamically favorable below 360, 350, 300, 285, 235, 277, and 251 K, respectively at 1 atm pressure. From PDOS analysis, it is observed that the 1s orbital of H overlaps with 3d orbital of Ti atom. The highest H2 desorption temperature is observed for the C12B4N4Ti nanocage, and the lowest for C10B10Ti, aligning well with the calculated adsorption energy values. As H2 desorption temperature is high, the stability of Ti-doped nanocages at high temperature (634 K) is confirmed using ab initio molecular dynamics simulations. Bader's quantum theory in atoms in molecules is used to prove the weak non-covalent interaction between all the atoms.
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•C20Ti and its B, N or B and N substituted derivatives are considered for H2 storage.•Substitution of heteroatoms in C20Ti enhances the binding strength of Ti atom.•B10C10Ti is the most stable among the eight Ti doped nanocages considered.•Favorable H2 adsorption for wide range of pressure at room temperature.•H2 molecule shows better affinity with C12B4N4Ti.
Two new 1,3,4-thiadiazole derivatives of ibuprofen and ciprofloxacin namely {(5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine)} 1 and ...{(3-(5-amino-1,3,4-thiadiazol-2-yl)-1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one)} 2 were synthesized and characterized by spectroscopic and elemental analysis. DFT and molecular docking were done initially for theoretical binding possibilities of the investigated compounds. In vitro DNA binding investigations were carried out with UV–visible spectroscopic, fluorescence spectroscopic, cyclic voltammetric (CV) experiments under physiological conditions of the stomach (4.7) and blood (7.4) pH and at normal body temperature (37 °C). Both theoretical and experimental results suggested spontaneous and significant intercalative binding of the compounds with DNA. Kinetic and thermodynamic parameters (Kb, ΔG) were evaluated greater for compound 2 which showed comparatively more binding and more spontaneity of 2 than 1 to bind with DNA at both pH values. Binding site sizes were found greater (n > 1) and revealed the possibility of other sites for interactions along with intercalation. Overall results for DNA binding were found more significant for 2 at Stomach (4.7) pH. Viscometric studies further verified intercalation as a prominent binding mode for both compounds. IC50 values obtained from human hepatocellular carcinoma (Huh-7) cell line studies revealed 2 as potent anticancer agent than 1 as value found 25.75 μM (lesser than 50 μM). Theoretical and experimental DNA binding studies showed good correlation with cancer cell (Huh-7) line activity of 1 and 2 and further suggested that these compounds could act as potential anti-cancer drug candidates.
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•Ibuprofen and ciprofloxacin derivatives of 1, 3, 4-thiadiazole 1 &2.•Theoretical binding possibilities of 1 and 2 by DFT and molecular docking.•Intercalative DNA binding greater at pH 4.7; Kb of 2 > 1; consistency in Kb and ΔG.•Anticancer potential of 1 and 2 for Huh-7 cancer cell line.•Correlation between theoretical, experimental and biological findings.
This study focuses on source term inversion in fractional partial differential equations, specifically applied to photoacoustic imaging. This work contributes to advancing imaging techniques and ...provides practical insights for medical diagnostics and materials characterization. Our aim in this paper is to develop an accurate method for recovering the location and the shape of a laser excitation source from partial boundary data. To achieve this, we reformulate our inverse problem as an optimization challenge. We utilize topological sensitivity analysis to establish an asymptotic expansion of a relevant shape function. These theoretical findings form the basis for a rapid and precise detection algorithm. Additionally, we present several numerical experiments that demonstrate the effectiveness and accuracy of our proposed approach.
Graphene materials have unique structures and outstanding thermal, optical, mechanical and electronic properties. In the last decade, these materials have attracted substantial interest in the field ...of nanomaterials, with applications ranging from biosensors to biomedicine. Among these applications, great advances have been made in the field of antibacterial agents. Here, recent advancements in the use of graphene and its derivatives as antibacterial agents are reviewed. Graphene is used in three forms: the pristine form; mixed with other antibacterial agents, such as Ag and chitosan; or with a base material, such as poly (N‐vinylcarbazole) (PVK) and poly (lactic acid) (PLA). The main mechanisms proposed to explain the antibacterial behaviors of graphene and its derivatives are the membrane stress hypothesis, the oxidative stress hypothesis, the entrapment hypothesis, the electron transfer hypothesis and the photothermal hypothesis. This review describes contributions to improving these promising materials for antibacterial applications.
Recent advancements in using graphene derivatives as antibacterial agents are reviewed. The mechanisms put forward to explain their antibacterial behaviors are various, mainly including membrane stress, oxidative stress, photothermal, entrapment isolation and electron transfer hypothesis. The goal of this review is to contribute to the improvement of the functionality of these promising materials in antibacterial applications.
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