Interaction of Caffeine Molecular Associates with Water: Theory and Experiment

Results of a Monte Carlo simulation of the association process of caffeine (1,3,7-trimethyl-2,6-dioxipurine) in water are presented. Simulation was performed in a cluster approximation ; the system contained 200 water molecules. The nature of the stabilization of caffeine stacking associates in water was considered. Hydrophobic behaviour of methyl group s during association of caffeine molecules in water is shown. The peculiarity of interaction of caffeine associates with water in dependence on the starting geometry of dimer is considered. Results of the simulation on the caffeine association process are compared to experimental data from the study of aqueous solutions of caffeine

Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo₆I₈}⁴⁺ metal clusters

Silica nanoparticles (SNPs) doped by hexanuclear molybdenum cluster complexes [{Mo₆X₈}L₆]n (X = Cl, Br, or I; L = various inorganic or organic ligands) have been recently suggested as materials with a high potential for biomedical applications due to both the outstanding photoluminescent properties and the ability to efficiently generate singlet oxygen upon photoirradiation. However, no studies were undertaken so far to prove this concept. Therefore, here we examined the potential of photoluminescent SNPs doped by {Mo₆I₈}⁴⁺ for such applications as bioimaging and photodynamic therapy using human epidermoid larynx carcinoma (Hep-2) cell line as a model. Our results demonstrated both: (i) significant luminescence from cells with internalised molybdenum cluster doped SNPs combined with the low cytotoxicity of particles in the darkness and (ii) significant cytotoxicity of the particles upon photoirradiation. Thus, this research provides strong experimental evidence for high potential of molybdenum cluster doped materials in such biomedical applications as optical bioimaging, biolabeling and photodynamic therapy

A comparative study of hydrophilic phosphine hexanuclear rhenium cluster complexes’ toxicity

Octahedral rhenium cluster compound Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] has recently emerged as a very promising X-ray contrast agent for biomedical applications. However, the synthesis of this compound is rather challenging due to difficulty to control the hydrolysis of initial P(C2H4CN)3 ligand during the reaction process. Therefore, in this report we compare the in vitro and in vivo toxicity of Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] with those of related compounds featuring fully hydrolysed form of the phosphine ligand, namely Na2H14[{Re6Q8}(P(C2H4COO)3)6] (Q = S or Se). Our results demonstrate that cytotoxicity and acute in vivo toxicity of the complex Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6] solutions were considerably lower than those of compounds with fully hydrolysed ligand P(C2H4COOH)3. Such behavior can be explained by the higher osmolality of Na2H14[{Re6Q8}(P(C2H4COO)3)6] versus Na2H8[{Re6Se8}(P(C2H4CONH2)(C2H4COO)2)6]

Combined Use of Amentoflavone and Ledipasvir Could Interfere with Binding of Spike Glycoprotein of SARS-CoV-2 to ACE2: The Results of Molecular Docking Study

In this study we used molecular docking method to test 248 drugs related to the virus research against spike glycoprotein of SARS-CoV-2. For ten top-ranked drugs the binding sites and interactions with spike glycoprotein were analyzed in detail. The best-scored ligand is the natural biflavonoid amentoflavone. Nine of twelve top-ranked ligands are drugs used for hepatitis C treatment. Among them are ledipasvir, paritaprevir, elbasvir, simeprevir, velpatasvir, glecaprevir and pibrentasvir. The two first-ranked ligands (amentoflavone and ledipasvir) have different binding sites, so their combined use may be effective, but the careful testing is required. We encourage other researchers to explore the combination of amentoflavone and ledipasvir against SARS-CoV-2 in vitro and in vivo.</p

Sequence-specific transitions of the torsion angle gamma change the polar-hydrophobic profile of the DNA grooves: implication for indirect protein–DNA recognition

<div><p>Variations of the shape and polarity of the DNA grooves caused by changes of the DNA conformation play an important role in the DNA readout. Despite the fact that non-canonical <b><i>trans</i></b> and <b><i>gauche</i></b>- conformations of the DNA backbone angle <i>γ</i> (O5′–C5′–C4′–C3′) are frequently found in the DNA crystal structures, their possible role in the DNA recognition has not been studied systematically. In order to fill in this gap, we analyze the available high-resolution crystal structures of the naked and complexed DNA. The analysis shows that the non-canonical <i>γ</i> angle conformations are present both in the naked and bound DNA, more often in the bound vs. naked DNA, and in the nucleotides with the A-like vs. the B-like sugar pucker. The alternative angle <i>γ</i> torsions are more frequently observed in the purines with the A-like sugar pucker and in the pyrimidines with the B-like sugar conformation. The minor groove of the nucleotides with non-canonical <i>γ</i> angle conformation is more polar, while the major groove is more hydrophobic than in the nucleotides with the classical <i>γ</i> torsions due to variations in exposure of the polar and hydrophobic groups of the DNA backbone. The propensity of the nucleotides with different <i>γ</i> angle conformations to participate in the protein–nucleic acid contacts in the minor and major grooves is connected with their sugar pucker and sequence-specific. Our findings imply that the angle <i>γ</i> transitions contribute to the process of the protein–DNA recognition due to modification of the polar/hydrophobic profile of the DNA grooves.</p></div

Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model.

Oncolyic virotherapy is one of the modern experimental techniques to treat human cancers. Here we studied the antitumor activity of wild-type Newcastle disease virus (NDV) isolates from Russian migratory birds. We showed that NDV could selectively kill malignant cells without affecting healthy cells. We evaluated the oncolytic effect of 44 NDV isolates in 4 histogenetically different human cell lines (HCT116, HeLa, A549, MCF7). The safety of the isolates was also tested in normal peripheral blood mononuclear (PBMC) cells. The viability of tumor cell lines after incubation with NDV isolates was evaluated by MTT. All cell lines, except for normal PBMC primary cells, had different degrees of susceptibility to NDV infection. Seven NDV strains had the highest oncolytic activity, and some NDV strains demonstrated oncolytic selectivity for different cell lines. In vivo, we described the intratumoral activity of NDV/Altai/pigeon/770/2011 against subcutaneous non-small cell lung carcinoma using xenograft SCID mice model. All animals were responsive to therapy. Histology confirmed therapy-induced destructive changes and growing necrotic bulk density in tumor tissue. Our findings indicate that wild-type NDV strains selectively kill tumor cells with no effect on healthy PBMC cells, and intratumoral virotherapy with NDV suppresses the subcutaneous tumor growth in SCID mice

The oncolytic effect of NDV isolates on human tumor cell line in vitro.

<p>(A) Colorectal cancer HCT116 cells, (B) cervical cancer HeLa cells, (C) non-small cell lung cancer A549 cells. The MTT analysis on the 4^th day after infection (2, 8 and 16 HAU per 10.000 cells).</p

<i>In vivo</i> NDV therapy resulted in inhibition of subcutaneous tumor nodes of non-small-cell lung A549 carcinoma-bearing SCID mice.

<p>(a) Mice from control group receiving PBS injections. (b) Mice intratumorally injected with four doses of NDV/Altai/pigeon/770/2011 (7 lgTCID50/100μl) during 4 days. Areas with tumor nodules are denoted by arrows. 15^th day after virotherapy (38^th day of tumor growth).</p

NDV treatment results in tumor necrosis in non-small-cell lung carcinoma–bearing mice.

<p>Male SCID mice bearing subcutaneous human non-small-cell lung carcinoma A549 nodules were infected with NDV/Altai/pigeon/70/2011 (7 lgTCID50/100μl) in series of intratumoral injections (one injection/day during 4 days). Mice (n = 5) were sacrificed 5, 10 and 15 days post-infection. Tumor sections were stained with hematoxylin and eosin (H&E) and microscopically analyzed for tumor necrosis. Massive sites of destructive necrosis on the 10^th day after virotherapy (a) vs tumor tissue of the control group of mice, receiving PBS injections (b). Areas of necrosis are denoted by arrows. Magnification ×20.</p

The viability of human tumor cell lines after NDV-infection.

<p>The viability of (a) HCT116, (b) HeLa, (c) A549 and (d) MCF7 cell lines after incubation with wild-type NDV isolates, 4^th day after viral infection. The MTT results of cells incubated with fresh medium were taken as control (100%).</p