- Design, synthesis and biological evaluation of novel α-aminophosphonate oxadiazoles via optimized iron triflate catalyzed reaction as apoptotic inducers. [Journal Article]
- EJEur J Med Chem 2019 Jul 11; 180:310-320
- α-aminophosphonate oxadiazoles (5a-m) were prepared in high yields by reacting of 1,3,4-oxadiazole acetohydrazide (3) with appropriate aldehydes and diethyl phosphite under Kabachnik-Fields condition…
α-aminophosphonate oxadiazoles (5a-m) were prepared in high yields by reacting of 1,3,4-oxadiazole acetohydrazide (3) with appropriate aldehydes and diethyl phosphite under Kabachnik-Fields conditions using Iron triflate as a catalyst. The reaction conditions were optimized using D-optimal experimental design. Possible reaction mechanisms were considered, and structures of the new products were based upon compatible elementary and spectroscopic evidence. In vitro antitumor activities of these compounds were evaluated against human cancer cell lines of colon (HCT116), breast (MCF7) and liver (HepG2) and compared with anticancer drug, Doxorubicin, employing standard MTT assay. Compounds 5i and 5l demonstrated good antiproliferative activities against HCT116 tumor cells comparable to doxorubicin with low cytotoxicity towards normal fetal colon cell (FHC). Additionally, their capacity to activate apoptosis cascade was studied in HCT116 cell line by investigating the activation of proteolytic caspases cascade, the levels of Cytochrome C, Bax and Bcl-2. Active caspase-3 level was enhanced by 6-8-folds in HCT116 cell line when stimulated with compounds 5i and 5l compared to the control. The level of Caspases 8 & 9 was also increased signifying that intrinsic and extrinsic pathways are both activated. They also induced Bax and down regulated Bcl-2 protein level in addition to over-expressing Cytochrome C level in HCT116 cell line. Also, HCT116 cell cycle was mainly arrested at the Pre-G1 and G2/M phases when treated with compounds 5i and 5l.
- Effect of curcumin derivatives on hen egg white lysozyme amyloid fibrillation and their interaction study by spectroscopic methods. [Journal Article]
- SASpectrochim Acta A Mol Biomol Spectrosc 2019 Jul 08; 223:117365
- Two novel Boc-L-isoleucine-functionalized curcumin derivatives have been synthesized and characterized, which exhibited enhanced solubility in water compared with the natural curcumin. The solubility…
Two novel Boc-L-isoleucine-functionalized curcumin derivatives have been synthesized and characterized, which exhibited enhanced solubility in water compared with the natural curcumin. The solubility could reach 2.12mg/mL for the monosubstituted compound and 3.05mg/mL for the disubstituted compound, respectively. Their anti-amyloidogenic capacity on the model protein, hen egg white lysozyme (HEWL), was examined in aqueous solution. ThT fluorescence assay showed that the operation concentration was only 0.5mM when the inhibition ratio was above 70%. Meanwhile, the inhibitory capacity of monosubstituted curcumin derivative on the formation of HEWL amyloid fibrils was found to be superior to that of disubstituted derivative, suggesting that the phenolic hydroxyl group might contribute to the anti-amyloidogenic activity. Interaction study showed that both curcumin derivatives could bind with HEWL near tryptophan residues and form new ground-state complex before HEWL self-assemblies into amyloid fibrils and thus inhibits the formation of amyloid fibrils. Both of the two cucumin derivatives have displayed low cytotoxicity with HeLa cell.
- Spectro-electrochemistry of ciprofloxacin and probing its interaction with bovine serum albumin. [Journal Article]
- BBioelectrochemistry 2019 Jul 09; 130:107330
- In the present investigation the electrochemical behaviour of the drug, Ciprofloxacin (Cf) and its interaction with the Bovine Serum Albumin (BSA) is reported. UV-Visible Spectroscopy (UV-Vis) and Sp…
In the present investigation the electrochemical behaviour of the drug, Ciprofloxacin (Cf) and its interaction with the Bovine Serum Albumin (BSA) is reported. UV-Visible Spectroscopy (UV-Vis) and Spectro-electrochemical measurements were carried out to quantify the charge transfer process in Cf. Analysis of the results obtained from cyclic voltammetry (CV) measurements indicated the electrochemical oxidation of Cf followed mixed adsorption and diffusion control process. The spectro-electrochemical investigations were carried out and the modification of the spectral peaks were monitored to obtain the mechanism of the electrochemical oxidation process of Cf. Interaction of Cf with Bovine Serum Albumin (BSA) were investigated using electrochemical, spectroscopic and spectro-electrochemical experiments. Important electro-kinetic parameters like; the electron transfer property, binding constant and diffusivity of the Cf/BSA complex were investigated. Electrochemistry with an ultra-microelectrode was utilised to investigate the diffusivity of the drug and its complex with BSA, which supports the strong binding of Cf with BSA.
- Topoisomerase inhibition and albumin interaction studies of acridine-thiosemicarbazone derivatives. [Journal Article]
- IJInt J Biol Macromol 2019 Jul 16
- In the present study, acridine-thiosemicarbazones (ATD) derivatives were tested for their interaction properties with BSA through UV-Vis absorption and fluorescence spectroscopic studies. Both hyperc…
In the present study, acridine-thiosemicarbazones (ATD) derivatives were tested for their interaction properties with BSA through UV-Vis absorption and fluorescence spectroscopic studies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated after the derivatives were added to the BSA. Values for the binding constant (Kb) ranged from 1.62 × 104 to 8.71 × 105 M-1 and quenching constant (KSV) from 3.46 × 102 to 7.83 × 103 M-1 indicating a good affinity to BSA protein. Complementary, two compounds were selected to assess their inhibition activity against topoisomerase IIα enzyme, of which derivative 3a presented the best result. Moreover, to evaluate protein-ligand interactions, as well as the antitopoisomerase potential of these compounds, tests of molecular modeling were performed between all compounds using the albumin and Topoisomerase IIα/DNA complex. Finally, in silico studies showed that all derivatives used in this research displayed good oral bioavailability potential.
- Anticancer altretamine recognition by bovine serum albumin and its role as inhibitor of fibril formation: Biophysical insights. [Journal Article]
- IJInt J Biol Macromol 2019 Jul 16
- Binding of anticancer drug altretamine with bovine serum albumin (BSA) and its inhibitory effect on fibrillation of the protein has been studied by using a combination of spectroscopic and calorimetr…
Binding of anticancer drug altretamine with bovine serum albumin (BSA) and its inhibitory effect on fibrillation of the protein has been studied by using a combination of spectroscopic and calorimetric methods. Altretamine is observed to bind with BSA with a moderate binding affinity of the order of 105, which is weakly temperature dependent. Circular dichroism, fluorescence spectroscopic and dynamic light scattering methods have been employed to monitor the conformational change in the protein. Time correlated single photon counting measurements have confirmed ground state complexation of the drug with the protein. Docking studies have led to identification of binding sites on BSA at site III in domain IB. Thioflavin T (ThT) fluorescence emission has been used as a tool to monitor the formation of fibrils/aggregates in BSA. It is observed that anticancer drug altretamine can also act as an inhibitor of fibrillation in BSA and hence can be useful in the treatment of neuro-degenerative diseases. Differential scanning calorimetry has been employed to study the thermal transitions of BSA at different stages of the fibrillation process with and without altretamine to obtain insights into the extent of stabilisation provided by the drug to the protein in native, nucleation/elongation and matured state in the fibrillation process.
- Effects of the antidepressant medication duloxetine on brain metabolites in persistent depressive disorder: A randomized, controlled trial. [Journal Article]
- PlosPLoS One 2019; 14(7):e0219679
- CONCLUSIONS: These findings, taken together, suggest that PDD is not a direct consequence of elevated NAA concentrations, but that a more fundamental pathophysiological process likely causes PDD and determines the severity of its symptoms. The findings also suggest that although duloxetine normalized NAA concentrations in patients, it did so by modulating the severity of depressive symptoms. Medication presumably reduced depressive symptoms through other, as yet unidentified, brain processes.
- Three Ways Isolable Carbenes Can Modulate Emission of NH-Containing Fluorophores. [Journal Article]
- JAJ Am Chem Soc 2019 Jul 19
- Fluorescent molecules and materials that exhibit emission changes in response to analytes are of great interest across multiple disciplines. Herein, we investigate the response of NH-containing fluor…
Fluorescent molecules and materials that exhibit emission changes in response to analytes are of great interest across multiple disciplines. Herein, we investigate the response of NH-containing fluorophores carbazole and 2-phenylbenzimidazole (Ph-BIM) with two representative isolable singlet carbenes. Specifically, N-heterocyclic carbene 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) and cyclic (alkyl)(amino)carbene (2,6-diisopropylphenyl)-4,4-diethyl-2,2-dimethyl-pyrrolidin-5-ylidene (Et CAAC) were discovered to afford three different types of reaction products with carbazole and Ph-BIM. Depending on the reaction pair, hydrogen bonding (1), NH-insertion (2,3), or proton transfer (4) products can be isolated, each displaying variable photophysical responses. These products have been structurally authenticated by single crystal X-ray diffraction and NMR spectrometric methods. Studies of the solution state behavior of 1-4 reveals that these adducts are labile and can reversibly dissociate to free carbenes and fluorophores to varying extents. These equilibria produce concentration dependent solution state behavior as identified and quantified via UV-visible absorption, emission, 1H DOSY, and NMR spectroscopic measurements.
- Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR. [Journal Article]
- ACAngew Chem Int Ed Engl 2019 Jul 19
- Precise nanoscale distance measurements by pulsed Electron Paramagnetic Resonance (EPR) play crucial role in structural studies of biomolecules and their complexes. The properties of spin labels used…
Precise nanoscale distance measurements by pulsed Electron Paramagnetic Resonance (EPR) play crucial role in structural studies of biomolecules and their complexes. The properties of spin labels used in this approach are of paramount importance, since they determine the sensitivity limits, attainable distances and proximity to biological conditions, including physiological temperatures. Herewith, we propose and validate the use of photoexcited fullerenes as spin labels for pulsed dipolar (PD) EPR distance measurements. Hyperpolarization and narrower spectrum of fullerenes compared to other triplets (e.g., porphyrins) boost the sensitivity, and superior relaxation properties allow PD EPR measurements up to a near-room temperature. The capabilities of new approach are demonstrated using fullerene-nitroxide and fullerene-triarylmethyl pairs, as well as supramolecular complex of fullerene with nitroxide-labeled protein. Therefore, photoexcited triplet fullerenes can be considered as new spin labels with the outstanding spectroscopic properties for future structural studies of biomolecules.
- Ultra-thin NaCl films as protective layers for graphene. [Journal Article]
- NNanoscale 2019 Jul 19
- The ageing of graphene is an important issue that limits its technological applications. Capping layers are a good option for circumventing this problem. In this work, we propose the use of ultra-thi…
The ageing of graphene is an important issue that limits its technological applications. Capping layers are a good option for circumventing this problem. In this work, we propose the use of ultra-thin NaCl films as easily-removable protective layers. We have carried out a detailed characterization of the NaCl/graphene interface on metal substrates, namely Cu(111) and Ir(111), by means of complementary microscopy, electron diffraction and spectroscopic techniques. Interestingly, we show that NaCl neither interacts in a chemical way with graphene nor intercalates through it. We demonstrate that the NaCl film is stable under ambient conditions, protecting the graphene surface from oxidation. In addition, after removing the protective layer, graphene remains intact.
New Search Next
- Bicyclic lactones from the octocoral Dendronephthya mucronata. [Journal Article]
- NPNat Prod Res 2019 Jul 19; :1-5
- The MeOH extract of the Vietnamese octocoral Dendronephthya mucronata afforded four bicyclic lactones (1-4), including three new compounds namely dendronephthyones A-C (1-3), after subjecting it on v…
The MeOH extract of the Vietnamese octocoral Dendronephthya mucronata afforded four bicyclic lactones (1-4), including three new compounds namely dendronephthyones A-C (1-3), after subjecting it on various chromatographic separations. The structures of the isolated compounds were established by spectroscopic experiments including 1D, 2D NMR, CD and HR-QTOF-MS. In addition, compounds 1-4 were found to exhibit selective cytotoxicity against the HeLa human cancer cell line with IC50 values of 32.48 ± 2.15, 30.12 ± 1.86, 35.14 ± 1.57 and 14.45 ± 1.34 μM, respectively.