The title compound, C16H10, crystallizes with four unique mol-ecules, designated 1-4, in the asymmetric unit of the monoclinic unit cell. None of the mol-ecules is planar, with the benzene rings of mol-ecules 1-4 inclined to one another at angles of 42.41 (4), 24.07 (6), 42.59 (4) and 46.88 (4)°, respectively. In the crystal, weak C-H⋯π(ring) interactions, augmented by even weaker C C-H⋯π(alkyne) contacts, generate a three-dimensional network structure with inter-linked columns of mol-ecules formed along the c-axis direction.
The coumarin ring system in the title asymmetric alkyne, C18H12O2, is approximately planar (r.m.s. deviation of the 11 non-H atoms = 0.048 Å), and is inclined with respect to the methyl-benzene ring, forming a dihedral angle of 33.68 (4)°. In the crystal, supra-molecular zigzag chains along the c-axis direction are formed via weak C-H⋯O hydrogen bonds, and these are connected into double layers via weak C-H⋯π inter-actions; these stack along the a axis.
Introduction: The purpose of this study was to evaluate inter-session repeatability, inter-examiner
reproducibility and inter-device agreement of corneal power measurements from manual keratometer,
autokeratometer, topographer, Pentacam high resolution and IOLMaster. Methods: Two sets of mean
corneal power measurements (n=40) were compared for inter-session repeatability and inter-examiner
reproducibility in each instrument. Repeatability and reproducibility were evaluated by within-subject
standard deviation (Sw), coefficient of variation (COV) and intraclass correlation coefficient (ICC). A oneway
repeated measures analysis of variance was conducted to compare differences in the corneal power
between each instrument pair. The Bland and Altman analysis and Pearson’s correlation were employed to
assess agreement and determine strength of relationship between measurements. Results: There were no
significant differences in mean corneal power measurements between 2 different visits (p > 0.05). The Sw
and COV values between 2 visits were lower than 0.09 D and 0.20 % respectively. The ICCs were stronger
than 0.99 in all instruments. For reproducibility of each instrument, differences of the measurements
between 2 different examiners were also insignificant (p > 0.05). The Sw and COV values between 2
examiners were lower than 0.11 D and 0.23 % respectively. The ICCs were 0.99 and above in all instruments.
The 95% limit of agreement between instruments ranged from -0.29 to 1.13 D and the r-values were stronger
than 0.84. Conclusion: The corneal power measurements using these 5 instruments were repeatable and
reproducible. These instruments can also be used interchangeably, however the topographer should be used
with caution.
Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.
A highly convenient method has been developed for the synthesis of (prop-2-ynyloxy) benzene and its derivatives. Differently substituted phenol and aniline derivatives were allowed to react with propargyl bromide in the presence of K2CO3 base and acetone as solvent. The compounds were synthesized in good yields (53-85%). Low cost, high yields and easy availability of compounds helped in the synthesis. Electron withdrawing groups favor the formation of stable phenoxide ion thus in turn favors the formation of product while electron donating groups do not favor the reaction. Phenol derivatives gave good yields as compared to that of aniline. As aprotic polar solvents favor SN2 type reactions so acetone provided best solvation for the reactions. K2CO3 was proved to be good for the synthesis. Antibacterial, Antiurease and NO scavenging activity of synthesized compounds were also examined. 4-bromo-2-chloro-1-(prop-2-ynyloxy)benzene 2a was found most active compound against urease enzyme with a percentage inhibition of 82.00±0.09 at 100 µg/mL with IC50 value of 60.2. 2-bromo-4-methyl-1-(prop-2-ynyloxy)benzene 2d was found potent antibacterial against Bacillus subtillus showing excellent inhibitory action with percentage inhibition of 55.67±0.26 at 100 µg/ml wih IC50 value of 79.9. Based on results, it can be concluded that some of the synthesized compounds may have potential antiurease and antibacterial effects against several harmful substances.
Using two different hydrosilylation methods, low temperature thermal and UV initiation, silicon (111) hydrogenated surfaces were functionalized in presence of an OH-terminated alkyne, a CF3-terminated alkyne and a mixed equimolar ratio of the two alkynes. XPS studies revealed that in the absence of premeditated surface radical through low temperature hydrosilylation, the surface grafting proceeded to form a Si-O-C linkage via nucleophilic reaction through the OH group of the alkyne. This led to a small increase in surface roughness as well as an increase in hydrophobicity and this effect was attributed to the surficial etching of silicon to form nanosize pores (~1-3 nm) by residual water/oxygen as a result of changes to surface polarity from the grafting. Furthermore in the radical-free thermal environment, a mix in equimolar of these two short alkynes can achieve a high contact angle of ~102°, comparable to long alkyl chains grafting reported in literature although surface roughness was relatively mild (rms = ~1 nm). On the other hand, UV initiation on silicon totally reversed the chemical linkages to predominantly Si-C without further compromising the surface roughness, highlighting the importance of surface radicals determining the reactivity of the silicon surface to the selected alkynes.
The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has proven to be a pivotal advance in chemical ligation strategies with applications ranging from polymer fabrication to bioconjugation. However, application in vivo has been limited by the inherent toxicity of the copper catalyst. Herein, we report the application of heterogeneous copper catalysts in azide-alkyne cycloaddition processes in biological systems ranging from cells to zebrafish, with reactions spanning from fluorophore activation to the first reported in situ generation of a triazole-containing anticancer agent from two benign components, opening up many new avenues of exploration for CuAAC chemistry.
Aiming for glycolipid-based vesicles for targeted drug delivery, cationic Guerbet glycosides with spacered click functionality were designed and synthesized. The cationic charge promoted the distribution of the glycolipids during the formulation, thereby leading to homogeneously small vesicles. The positive surface charge of the vesicles stabilizes them against unwanted fusion and promotes interactions of the drug carriers with typical negative charge-dominated target cells. High bioconjugation potential of the functionalized glycolipids based on the copper-catalyzed azide alkyne cycloaddition makes them highly valuable components for targeted drug delivery systems.
Corn-cob cellulose supported poly(hydroxamic acid) Cu(II) complex was prepared by the surface modification of waste corn-cob cellulose through graft copolymerization and subsequent hydroximation. The complex was characterized by IR, UV, FESEM, TEM, XPS, EDX and ICP-AES analyses. The complex has been found to be an efficient catalyst for 1,3-dipolar Huisgen cycloaddition (CuAAC) of aryl/alkyl azides with a variety of alkynes as well as one-pot three-components reaction in the presence of sodium ascorbate to give the corresponding cycloaddition products in up to 96% yield and high turn over number (TON 18,600) and turn over frequency (TOF 930h-1) were achieved. The complex was easy to recover from the reaction mixture and reused six times without significant loss of its catalytic activity.
The marine soft corals Sarcophyton trocheliophorum crude extracts possessed antimicrobial activity towards pathogenic bacterial strains, i.e. Bacillus cereus, Salmonella typhi, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Bioassay-guided fractionation indicated that the antimicrobial effect was due to the presence of terpenoid bioactive derivatives. Further biological assays of the n-hexane fractions were carried out using turbidity assay, inhibition zone assay and minimum inhibitory concentration for investigating the growth-inhibition effect towards the Gram-positive and Gram-negative bacteria. The fractions were screened and the structure of the isolated compound was justified by interpretation of the spectroscopic data, mainly mass spectrometry (GC-MS). The structure was assigned as (5S)-3-[(3E,5S)-5-hydroxy-3-hepten-6-yn-1-yl]-5-methyl-2(5H)-furanone and was effective at concentrations as low as 0.20 mg/mL. The above findings, in the course of our ongoing research on marine products, may implicate that the profound anti-microbial activity of the S. trocheliophorum soft corals, inhabiting the red sea reefs, is attributed to the presence of growth-inhibiting secondary metabolites mainly terpenoids.
Introduction: Accelerants and fabrics are commonly used to spread fire attributable to their highly flammable prop- erties. Hence, having the ability to discriminate the different types of accelerants on various types of fabrics after fire and/or arson using the non-destructive Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spec- troscopy coupled with chemometric techniques appears forensically relevant. Methods: Six types of fabrics viz. cotton, wool, silk, rayon, satin, and polyester, were burnt completely with RON95 and RON97 gasoline as well as diesel. Subsequently, the samples were analyzed by ATR-FTIR spectroscopy followed by Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) for discriminating the different types of accelerants on such burned fabrics. Results: RON95 showed the fastest rate of burning on all fabric types. Results also revealed that while wool had the slowest burning rate for all the three different accelerants, polyester, cotton, and satin demon- strated the highest rate of burning in RON95, RON97, and diesel, respectively. FTIR spectra revealed the presence of alkane, alcohol, alkene, alkyne, aromatic, and amine compounds for all fabrics. The two dimensional PCA (PC1 versus PC2) demonstrated 71% of variance and it was improved by cross-validation through the three dimensional LDA technique with correct classification of 77.8%. Conclusion: ATR-FTIR spectroscopy coupled with chemometric techniques had enabled identification of the functional groups, as well as statistically supported discrimination of the different accelerants, a matter of relevance in forensic fire and arson investigations.
Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.
Lipopolysaccharide (LPS) induces apoptosis in murine macrophages through the autocrine secretion of tumor necrosis factor (TNF)-α and nitric oxide (NO). LPS-induced inflammation in murine macrophages is associated with hydrogen sulfide (H2S) production. In this present study, we reported the novel role of H2S in LPS-induced apoptosis and its underlying molecular mechanism specifically at late phases in murine macrophage cells. Stimulation of RAW 264.7 macrophages with LPS resulted in a time- and dose-dependent induction of apoptosis. We observed that the LPS-induced early apoptosis (associated with TNF-α secretion) in macrophages was not inhibited in the presence of H2S inhibitor (DL-propargylglycine), whereas early apoptosis was absent in the presence of TNF receptor antibody. Interestingly, LPS-induced late apoptosis paralleled with H2S production was reduced in the presence of H2S inhibitor but not with TNF receptor antibody. The late apoptotic events mediated by H2S and not the TNF-α induced early apoptosis correlated significantly with the induction of p53 and Bax expression in LPS-induced macrophages. Thus, it is possible that RAW 264.7 murine macrophages treated with LPS mediated early apoptosis through TNF-α and the late apoptotic events through the production of H2S.
In 2007, HIV treatment services were established in five main governorates out of twenty-two which resulted in low access to services and poor treatment outcomes. The main goal of this study was to evaluate and analyse the selected treatment outcomes of eight cohorts of PLHIV who were treated with cART during 2007-2014. The method used was a retrospective descriptive study of 1,703 PLHIV who initiated cART at five public health facilities. The results: Retention rate was less than 80%, male: female ratio 1.661, with a mean age of 35 years (±9.2 SD), 85% had been infected with HIV via heterosexual contact. 65% of patients presented with clinical stages 3 and 4, and 52% of them were initiated cART at a CD4 T-cell count ≤200 cells/mm. 61% of cART included Tenofovir and Efavirenz. TB treatment started for 5% of PLHIV, and 22% developed HIV-related clinical manifestations after cART initiation. 67% of PLHIV had experienced cART substitution. The mean AIDS-mortality rate was 15% and the mean LTFU rate was 16%. Conclusion: Although cART showed effectiveness in public health, mobilization of resources and formulation of better health policies are important steps toward improving access to cART and achieving the desired treatment outcomes.