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1.
Paclitaxel (PTX) is a well-known antitumor drug, widely utilized in the treatment of breast, ovarian, head, and neck tumors, among others. The low aqueous solubility (< 1.0 μg/mL; log P = 3.96) limits its use by intravenous route, and alternatives found for the marketed products are associated with high toxicity. Incorporation of PTX into lipid nanocarriers has been considered an interesting nontoxic alternative for this route, but drug loading is usually low. This study aimed to analyze the influence of the lipid composition and three different lipid nanosystems—solid lipid nanoparticles, nanostructured lipid carriers (NLCs), and nanoemulsion—in PTX encapsulation and its biological response. The three proposed systems were prepared by hot melt homogenization followed by ultrasonication. Among the blank formulations first prepared, NLC had the smallest size (74 ± 1 nm), with negative zeta potential (? 11.4 ± 0.1 mV). The incorporation of 0.10 mg/mL PTX into this NLC formulation yielded high and stable encapsulation (0.089 ± 0.003 mg/mL), also supported by polarized light microscopy and differential scanning calorimetry curves. NLC-PTX was very effective against MCF-7 (IC50 25.33 ± 3.17 nM) and MDA-MB-231 breast cancer cell lines (IC50 2.13 ± 0.21 nM), compared to free PTX (IC50 > 500 nM). In addition, no significant cytotoxicity was found against fibroblast cells. Taken together, these results demonstrated that PTX was successfully incorporated into NLC with appropriate physicochemical characteristics for intravenous administration, suggesting that the use of NLC as vehicle to incorporate PTX may be a promising strategy in the treatment of breast cancer.  相似文献   

2.
Metal-hydroxyquinoline-halogen (MqX, M?=?Cd, Cu; q?=?8-hydroxyquinoline; X?=?Cl, Br, I) nanowires are synthesized via a sonochemical-assisted method. The elemental analysis (EA), inductively coupled plasma-optical emission spectroscopy (ICP-AES), and X-ray photoelectron spectroscopy (XPS) support an M/q/X ratio of 1:1:1. The electron microscope images reveal a typical CdqX and CuqX nanowire diameter of 30–50 nm and a nanowire length of 400–600 nm. In addition, the synthesis of the MqX nanowires is only observed when there is an excess of halide ions (X/q molar ratio of 3 or greater). This halide deficiency results in the formation of micrometer-sized Mq2 sheets. We demonstrated the conversion of the MqX nanowires to Mq2 micro-sheets in an ultrasonic bath of 1 M 8-Hq ethanol solutions (50%, w/w) at 50 °C for 2 h, but not vice versa. The MqX nanowires exhibited excellent properties for photoluminescence, electrochemiluminescence (ECL), and photoelectrochemistry (PEC). The CdqBr and CdqI nanowires were coated onto a glass carbon and a fluorine-doped tin oxide glass electrode to develop the above ECL and PEC methods for the detection of H2O2 and Cu2+, respectively. In the range of 2 to 14 μM, the ECL intensity of the CdqBr nanowires was inversely proportional to the concentration of H2O2 with a detection limit of 0.26 μM. For Cu2+ sensing, the photocurrent of the CdqI nanowires exhibited a linear response to Cu2+ over the range of 2 to 16 μM of which a detection limit of 0.2 μM was observed.  相似文献   

3.
A new mixed ligand copper(II)-dipeptide complex with 2-(2′-pyridyl)benzothiazole (pbt), [Cu(Gly-L-leu)(pbt)(H2O)]·ClO4 (Gly-L-leu = Glycyl-L-leucine anion) was synthesized and characterized by various physico-chemical means. The DNA binding and cleavage properties of the complex investigated by viscosity, agarose gel electrophoresis and multi-spectroscopic techniques (UV, circular dichroism (CD) and fluorescence) showed that the complex was bound to CT-DNA through intercalation mode with moderate binding constant (K b = 3.132 × 104 M?1), and cleaved pBR322 DNA efficiently (~ 5 μM) in the presence of Vc, probably via an oxidative mechanism induced by ?OH. Additionally, the interaction of the complex with human serum albumin (HSA) was explored by UV-visible, CD, fluorescence, synchronous fluorescence and 3D fluorescence spectroscopy. The complex exhibits desired affinity to HSA through hydrophobic interaction. Moreover, the cytotoxicity of the complex against three human carcinoma cell lines (HeLa, HepG2 and A549) was evaluated by MTT assay, which showed that the complex had effective cytotoxicity and higher inhibition toward A549 cell lines with IC50 of 38.0 ± 3.2 μM.  相似文献   

4.
A series of new chiral 1,3,4-thiadiazole-based bis-sulfonamides 4a–4w and tri-sulfonamide analogue 5 was synthesized and evaluated as anti-HIV agents. The reaction of chiral amino acids 1 with sulfonyl chlorides 2, followed by subsequent reaction of resultant N-protected amino acids 2a–2f with thiosemicarbazide in the presence of excess phosphorous oxychloride afforded N-(1-(5-amino-1,3,4-thiadiazol-2-yl)alkyl)-4-arylsulfonamides 3a–3f. Treatment of 2a–2f with substituted sulfonyl chlorides in portions furnished the target bis-sulfonamide analogues 4a–4w in good yields, together with the unexpected 5. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 4s were the most active in inhibiting HIV-1 with IC50?=?9.5 μM (SI?=?6.6), suggesting to be a new lead in the development of an antiviral agent. Interestingly, compound 5 exhibited significant cytotoxicity of >?4.09 μM and could be a promising antiproliferative agent.  相似文献   

5.
A quinoline functionalized two novel fluorescent Schiff bases, N-(quinolin-2-ylmethylene) anthracen-1-amine (SB1) and 2-(quinolin-2-ylmethyleneamino) benzene thiol (SB2) were synthesized and confirmed by using 1H NMR, IR and GC-MS techniques. The spectroscopic properties were examined by absorption spectroscopy and fluorescence spectroscopy. The absorption and fluorescence spectra of the probes (SB1 and SB2) were measured in a variety of solvents. Both the compounds were tested for urease inhibitory activity. The synthesized compound SB2 proved to be the most effective screening for enzyme inhibitory activity with IC50?=?0.111 μM than SB1 (IC50?=?0.287 μM). Molecular docking studies were performed to delineate the binding affinity and conformational positions of chemical compounds within the active region of the target protein. In-vitro analysis depicts the potency of SB1 in free radical scavenging as compared to the reference drug vitamin C.  相似文献   

6.
In the present paper, the use of a carbon paste electrode modified with 1-(4-(1, 3-dithiolan-2-yl)-6, 7-dihydroxy-2-methyl-6, 7-dihydrobenzofuran-3-yl)ethanone (DDE) and TiO2 nanoparticles prepared by a simple and rapid method was described. The modified electrode showed excellent properties for electrocatalytic oxidization of epinephrine (EP), acetaminophen (AC) and folic acid (FA). The apparent charge transfer rate constant, k s?=?1.14 s?1, and transfer coefficient, α?=?0.54, for electron transfer between the modifier and carbon paste electrode were calculated. It has been found that under optimum condition (pH?=?7.0) in cyclic voltammetry, the oxidation of EP occurs at a potential about 280 mV less positive than that of an unmodified carbon paste electrode. The values of transfer coefficients (α?=?0.46), catalytic rate constant (k?=?1.2?×?104 M?1 s?1) and diffusion coefficient (D?=?2.70?×?10?5 cm2 s?1) were calculated for EP. Differential pulse voltammetry (DPV) exhibited two linear dynamic ranges of 0.5 to 50.0 μM and 50.0 to 1,000 μM for EP. This modified electrode is quite effective not only for the detection of EP, AC and FA but also for the simultaneous determination of these species in a mixture. The limit of detection for EP, AC and FA is 0.10, 1.80 and 2.36 μM, respectively.  相似文献   

7.
Nian  Si-Yun  Wang  Guo-Ping  Jiang  Zheng-Li  Xiao  Ying  Huang  Mo-Han  Zhou  Yi-Huan  Tan  Xiang-Duan 《Molecular diversity》2019,23(1):19-33

Most of reported steroidal FXR antagonists are restricted due to low potency. We described the design and synthesis of novel nonsteroidal scaffold SIPI-7623 derivatives as FXR antagonists. The most potent compound A-11 (IC50?=?7.8?±?1.1 μM) showed better activity compared to SIPI-7623 (IC50?=?40.8?±?1.7 μM) and guggulsterone (IC50?=?45.9?±?1.1 μM). Docking of A-11 in FXR’s ligand-binding domain was also studied.

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8.
Herein, we design and synthesized new fluorescein based derivatives by insitu formation of fluorescein ester and further treated with corresponding hydrazide and amine to yield respective compounds i.e. FB1, FB2, FB3 and FB4. The spectral purity and characterization was done by using IR, NMR and Mass spectroscopies. The synthesized derivatives were examined for their photophysical properties by using variety of organic solvents and results were discussed in details. The structural diversity of synthesized compounds motivate us to evaluate these compounds for urease inhibition. The compound FB3 (IC50?=?0.0456 μM) shows 100 fold more active against Jack bean urease than standard drug thiourea (IC50?=?4.7455 μM). Other synthesized compounds showed potent activity. Free radical percentage scavenging assay further supported the capacity of compounds to urease inhibition. While, molecular docking simulations helps to examine the molecular interactions of active compounds FB1, FB2, FB3 and FB4 within the binding site of urease enzyme.  相似文献   

9.
In the present work, gold nanocluster (GNC) induced by bovine serum albumin (BSA) was synthesized as a novel fluorescence probe to detect nitrite (NO2 ?) sensitively and selectively. The fluorescence of GNC was found to be quenched effectively by NO2 ?. Under the optimum conditions, it was found that the change of fluorescence intensity was proportional with the concentration of NO2 ? in the linear range of 0.1–50 μM (R?=?0.9990), with a detection limit (S/N?=?3) of 30 nM. The absorption spectroscopy, circular dichroism (CD), and X-ray photoelectron spectroscopy (XPS) studies were employed to discuss the quenching mechanism. In addition, the present approach was successfully applied in real water samples.  相似文献   

10.

A new series of quinolotacrine hybrids including cyclopenta- and cyclohexa-quinolotacrine derivatives were designed, synthesized, and assessed as anti-cholinesterase (ChE) agents. The designed derivatives indicated higher inhibitory effect on the acetylcholinesterase (AChE) with IC50 values of 0.285–100 µM compared to butyrylcholinesterase (BChE) with IC50 values of?>?100 µM. Of these compounds, cyclohexa-quinolotacrine hybrids displayed a little better anti-AChE activity than cyclopenta-quinolotacrine hybrids. Compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c'] diquinolin-6-one (6m) including 3-hydroxyphenyl and cyclohexane ring moieties exhibited the best AChE inhibitory activity with IC50 value of 0.285 µM. The kinetic and molecular docking studies indicated that compound 6m occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE as a mixed inhibitor. Using neuroprotective assay against H2O2-induced cell death in PC12 cells, the compound 6h illustrated significant protection among the assessed compounds. In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these quinolotacrine hybrids can be very encouraging AChE inhibitors to treat Alzheimer’s disease.

Graphic abstract

A novel series of quinolotacrine hybrids were designed, synthesized, and evaluated against AChE and BChE enzymes as potential agents for the treatment of AD. The hybrids showed good to significant inhibitory activity against AChE (0.285–100 μM) compared to butyrylcholinesterase (BChE) with IC50 values of?>?100 μM. Among them, compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c′] diquinolin-6-one (6 m) bearing 3-hydroxyphenyl moiety and cyclohexane ring exhibited the highest anti-AChE activity with IC50 value of 0.285 μM. The kinetic and molecular docking studies illustrated that compound 6 m is a mixed inhibitor and binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.

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11.

In an effort to discover potential cytotoxic agents, a series of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-dione derivatives (8an) were designed and synthesized in various steps with acceptable reaction procedures with quantitative yields and characterized by 1H NMR, 13C NMR, IR, HRMS and ESI–MS spectra. These newly synthesized novel derivatives were screened for their in vitro cell viability/cytotoxic studies against human breast cancer cell line (MCF-7) with various concentrations of 0.625 µM, 1.25 µM, 2.5 µM, 5 µM and 10 µM, respectively. The biological interpretation assay outcome was demonstrated in terms of cell viability percentage reduction and IC50 values against standard reference drug cisplatin. Based on these results, most of the derivatives exhibited promising cytotoxic activity. Among them, particularly compounds 8j (R1?=?OMe and R3?=?NO2) and 8e (R3?=?CF3) demonstrate remarkable cytotoxic activity with IC50 values 0.426 µM?±?0.455 and 0.608 µM?±?0.408, which are even better than the standard drug cisplatin 0.636 µM?±?0.458 and compounds 8m (R2?=?OMe and R3?=?OMe) and 8c (R3?=?OMe) exhibited closely equivalent IC50 values to the standard drug with IC50 values 0.95 µM?±?0.32 and 0.976 µM?±?0.313 and rest of the compounds exhibits moderate cytotoxic activity. Moreover, molecular modeling studies and ADME calculations of the novel synthesized derivatives are in adequate consent with the pharmacological screening results.

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12.
Niobium-doped MnO2/reduced graphene oxide (Nb-MnO2/RGO) composite has been successfully synthesized via a simple microwave radiation method. The samples were systematically studied by X-ray diffraction (XRD), thermogravimetric analysis (TG), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), transmission electron microscope (TEM), and electrochemical measurements. As the anode material for lithium-ion batteries, the Nb-MnO2/RGO (molar ratio of Mn/Nb?=?50:1) (NMG50) showed an outstanding reversible discharge capacity of 556.6 mAh g?1 after 50 cycles with a capacity retention of 77% at a charge-discharge rate of 0.1 A g?1 and the reversible discharge capacity can still retain 223.3 mAh g?1 at a current of 1 A g?1, which is much higher than those for Nb-MnO2/RGO (molar ratio of Mn/Nb?=?10:1) (NMG10) and undoped MnO2/RGO (MG). The improved electrochemical performance could be attributed to the proper amount of Nb doping, which could enhance both the conductivity and the structure stability of MnO2.  相似文献   

13.
In the present work TiO2 nanoparticles (NPs) have been dispersed into three different nematic liquid crystals (2020, 1823A and 1550C) in different concentration. The value of the birefringence (Δn) has been calculated by the transmitted intensity method at a 632.8 nm wavelength. NLC 2020 used in the present study is a high birefringent material (Δn = 0.44), NLC 1550C is a low birefringent material (Δn = 0.067) and NLC 1823A is a mid birefringent material (Δn = 0.14). An increased value of birefringence has been found after dispersion of TiO2 NPs in all three NLCs but this increment depends upon the concentration of the dopant material, temperature range and chemical character of the mixtures. It is suggested that this LC materials can be applicable in making of phase shifters, compensators and many more photonic devices.  相似文献   

14.
This is the first report of inactivation of xyloglucanase from Thermomonospora sp by pepstatin A, a specific inhibitor towards aspartic proteases. The steady state kinetics revealed a reversible, competitive, two-step inhibition mechanism with IC 50 and K i values of 3.5?±?0.5 μM and 1.25?±?0.5 μM respectively. The rate constants determined for the isomerization of EI to EI* and the dissociation of EI* were 14.5?±?1.5?×?10?5?s?1 and 2.85?±?1.2?×?10?8?s?1 respectively, whereas the overall inhibition constant K i * was 27?±?1 nM. The conformational changes induced upon inhibitor binding to xyloglucanase were monitored by fluorescence analysis and the rate constants derived were in agreement with the kinetic data. The abolished isoindole fluorescence of o-phthalaldehyde (OPTA)-labeled xyloglucanase and far UV analysis suggested that pepstatin binds to the active site of the enzyme. Our results revealed that the inactivation of xyloglucanase is due to the interference in the electronic microenvironment and disruption of the hydrogen-bonding network between the essential histidine and other residues involved in catalysis.  相似文献   

15.
In this study, we have developed a novel nanoprobe for H2O2 based on the conjugation of CdTe@ZnS quantum dots (QDs) to different metal tetraamino-phthalocyanine (MTAPc): (M?=?(OAc)Al, {OAc?=?acetate}, Ni and Zn). Chemical coordination of the QDs to the MTAPc resulted in the fluorescence “switch off” of the linked QDs which was associated with Förster resonance energy transfer (FRET). In the presence of varying concentration of H2O2, the fluorescence of the linked QDs was progressively “switched on” and the FRET mechanism between the QDs and the MTAPc was disrupted. The sensitivity/limit of detection of the nanoprobe followed the order: QDs-ZnTAPc (2.2 μM)?>?QDs-NiTAPc (4.4 μM)?>?QDs-AlTAPc (9.8 μM) while the selectivity followed the order: QDs-NiTAPc?>?QDs-AlTAPc?>?QDs-ZnTAPc. The varying degree of sensitivity/selectivity and mechanism of detection is discussed in detail.  相似文献   

16.
In this paper, a selective and sensitive sensor for the determination of p-aminophenol (PAP) was developed by grafting molecularly imprinted polymers (MIPs) on the surface of silica-coated CdTe quantum dots (CdTe@SiO2@MIPs). The obtained CdTe@SiO2@MIPs were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and fluorescence spectroscopy. The fluorescence intensity of CdTe@SiO2@MIPs was more strongly quenched by PAP than that of the structural analogues of PAP. Under the optimal conditions, the fluorescence intensity of the CdTe@SiO2@MIPs decreased sensitively with the increase of PAP concentration in the range of 0.05–50 μM. The limit of detection was 0.02 μM (3σ/K sv). The sensor was successfully used to determine PAP in tap and lake water samples, and the average recoveries of PAP at various spiking levels ranged from 97.33 % to 103.3 % with relative standard deviations below 20 %.  相似文献   

17.
Zinc oxide microrods with controlled diameter were prepared without the addition of template and additive by a simple hydrothermal route only using Zn(CH3COO)2·2H2O as a precursor. The products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron diffraction (ED). The crystal structure of prepared ZnO microrods is hexagonal phase polycrystalline with zincite structure. With the increase of the precursor concentration from 0.05 M to 0.6 M, the diameter of the ZnO microrods increased from 1 μm to 5 μm. A localized oriented attachment mechanism was prepared to account for the formation of ZnO microrods. The gas-sensing performance experiments indicated that the prepared ZnO microrods exhibited highly sensitive, selective gas-sensing properties, and good stability to acetone vapor. The response and recovery time of ZnO-based gas sensor to 100 ppm acetone vapor are 12 s and 18 s, respectively. The mechanism of the ZnO-based sensor was investigated.  相似文献   

18.
A number of 2,4,5-triaryl-1H-imidazole derivatives were synthesized and evaluated for their antiproliferative activities against the growth of five cell lines including three non-small cell lung cancers (H460, H1299, and A549), one breast cancer (MCF-7), and one normal diploid embryonic lung cell line (MRC-5). Preliminary results indicated that both 2-(5-bromofuran-2-yl)-4,5-bis{4-[3-(dimethylamino) propoxy] phenyl}-1H-imidazole (10f) and 4,5-bis{4-[3-(dimethylamino)propoxy]phenyl}-2-(5-nitrofuran-2-yl)-1H -imidazole (10g) were selectively active against the growth of H1229 with an IC50 of less than 0.1???M, thus were more active than topotecan (IC50 >?10.0??? M). However, both 10f and 10g exhibited only marginal cytotoxicity against H460, A549, MCF-7, and MRC-5 requiring an IC 50 of at least 4.16???M. Our results also indicated that 10f induced H1299 cell cycle arrest at G0/G1 through the inactivation of p38 MAPK, JNK, ERK, as well as the expression of SIRT1 and survivin. These results suggested that 10f might have therapeutic potential against H1299 (non-small cell lung cancer cell).  相似文献   

19.
This study was designed to develop a highly selective and sensitive method towards fluorimetric sensing of cysteine (Cys) in water and human serum by using copper nanocluster. The Cys-CuNCs were characterized by scanning electron microscopy (SEM), FTIR, fluorescence and UV–Vis analysis. Spectroscopic evidences showed different intensities that were attributed to the different size of Cys-CuNCs. Enhancement in fluorescence intensity of copper nanoclusters with an increase in concentration of cysteine may enable them to be good candidates in detection systems. Selective recognition of cysteine in aqueous and serum samples was achieved during the formation of various copper nanoclusters (Cys-CuNCs) with different size. Under the optimized conditions, two linear range of the nanobiosensor for cysteine were between the 5 μM to 50 μM with detection limit of 2.4 μM and between 60 μM to 500 μM with detection limit of 55 μM. Fluorescence intensity increased with addition of cysteine concentration from 5 to 50 μM. The proposed low-cost nanobiosensor exhibited high reproducibility and good selectivity. It has been used also for the determination of cysteine in human serum samples with recoveries of 97–103 % and RSDs of 1.8–3.6 %  相似文献   

20.
New Ni(II) Schiff base complexes [{Ni(L)(H2O)Cl} where HL = 2-((pyridin-3-ylmethylene)amino)phenol] have been synthesized using the reflux and sonochemical methods. The nickel oxide NiO nanopowder was obtained from the metal complexes after calcination at 650 °C for 2 h. The Schiff base complexes and NiO powders were characterized in detail. The HL and its metal complexes were depicted high activity towards microorganism and breast carcinoma cells. The inhibitory activity against breast carcinoma (MCF-7) were detected with IC50 = 5.5, 12.5 and 9.6 for HL, complex (1) and complex (2), respectively. The optical band gap energy was 3.6, 3.0 and 2.37 eV for Ni complexes (1), (2) and NiO, respectively. The microstructure of the formed NiO powders appeared as cubic-like structure. Furthermore, magnetic properties of NiO sample were identified and paramagnetic property was found at a room temperature. The saturation magnetization and coercive force for the NiO sample were 0.47 emu/g and 42.68 Oe, respectively.  相似文献   

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