A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-(4-N, N-dimethylaminophenyl)-pyr- imidine-5-carbonitrile (AHDMAPPC), was synthesized. It was employed to investigate the binding in- teraction with ...A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-(4-N, N-dimethylaminophenyl)-pyr- imidine-5-carbonitrile (AHDMAPPC), was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin (BSA) in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites (n ≈ 1) were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change (AH), free energy (AG) and entropy change (AS) for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van't Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster's theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism (CD) and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.展开更多
Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-lo...Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.展开更多
Hydroxycinnamic acids (HCAs) possess numer- ous biological effects including antioxidant, antiallergic, antimicrobial, and immunomodulatory activities and due to these properties are widely used in folk medicine. Neve...Hydroxycinnamic acids (HCAs) possess numer- ous biological effects including antioxidant, antiallergic, antimicrobial, and immunomodulatory activities and due to these properties are widely used in folk medicine. Nevertheless, they can interact with protein molecules and cause some structural and functional changes. The possib- ility of HCAs binding to bovine serum albumin (BSA) under physiological conditions was inve- stigated by the UV-VIS absorption spectroscopy and fluorescence quenching method. Apart from rosmarinic acid, all tested HCAs quenched tryptophan fluorescence of BSA in the studied range of concentrations (0-20 μM) mainly by static quenching mechanism (formation of non- fluorescent HCA-BSA complexes). The binding constants, number of binding sites and free energy changes were determined. The binding affinities of HCAs were ranked in the order: chlorogenic acid > sinapic acid ≥ caffeic acid > ferulic acid > o-coumaric acid > p-coumaric acid ≥ m-coumaric acid, which was confirmed by spectral overlaps of BSA emission spectrum with absorption spectrum of HCA. All free energy changes possessed negative sign indicating the spontaneity of HCA-BSA interaction.展开更多
Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advance...Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.展开更多
The interaction of baicalein with bovine serum albumin(BSA) was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of...The interaction of baicalein with bovine serum albumin(BSA) was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 10~5 M^(-1) from fluorescence quenching studies.Negative ΔH°(-5.66 + 0.14 kJ/mol) and positive(ΔS°)(+ 79.96 + 0.65J/mol K) indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°.The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate(SDS) due to probable hydrophobic association of baicalein with SDS,resulting in a negative ΔS°(-40.65 + 0.87 J/mol K).Matrix-assisted laser desorption ionization/time of flight(MALDI-TOF) experiments indicate a 1:1 complexation between baicalein and BSA.The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements.It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA.The presence of metal ions(Ag~+,Mg^(2+),Ni^(2+),Mn^(2+),Co^(2+) and Zn^(2+)) increased the binding affinity of ligand towards BSA.The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism(CD) and Fourier transform infrared(FT-IR) spectroscopic techniques.Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1(subdomain MA) of BSA.展开更多
The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively ...The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.展开更多
Objective: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). Methods: We retrospectively analyzed the short-term ...Objective: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). Methods: We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results: Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in I0 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-flee survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). Conclusions: The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.展开更多
The binding mechanism of the interactions of halide ions (F–, Br– and I–) with bovine serum albumin (BSA) and hemoglobin (Hb) were studied at different temperatures, by using ion-selective electrodes. The experimen...The binding mechanism of the interactions of halide ions (F–, Br– and I–) with bovine serum albumin (BSA) and hemoglobin (Hb) were studied at different temperatures, by using ion-selective electrodes. The experimental data were treated according to Klotz equation, and the number of binding sites and the binding constants were determined. The results show that the binding sites of F– on protein molecules are more than those of Br– and I–. Additionally, the number of the binding sites for halide ions on protein molecules increases with increasing temperature. This study also indicates that the binding constants for the interactions of halide ions with proteins gradually decrease as the size of halide ions and temperature increases. These behaviors were reasonably interpreted with the structural and thermodynamic factors. The thermodynamic functions at different temperatures were calculated with thermodynamic equations, and the enthalpy change for the interactions were also determined by isothermal titration calorimetry (ITC) at 298.15 K, which indicate that the interactions of halide ions with proteins are mainly electrostatic interaction.展开更多
The binding of (-)-epigallocatechin-3-O-gallate (EGCG) to bovine serum albumin (BSA) were investigated for the first time with spectral methods, including fluorescence and absorption spectrometry under simulativ...The binding of (-)-epigallocatechin-3-O-gallate (EGCG) to bovine serum albumin (BSA) were investigated for the first time with spectral methods, including fluorescence and absorption spectrometry under simulative physiological conditions. A strong fluorescence quenching reaction of EGCG to BSA was observed. It was proved that the fluorescence quenching of BSA by addition of EGCG was a result of the formation of EGCG-BSA complex. The binding constant K and the number of binding sites n were determined at physiological conditions and three different temperatures with fluorescence quenching method. The binding distance R and transfer efficiency E between BSA and EGCG were also obtained according to Forster theory of non-radiation energy transfer. The effects of Al^3+, Cu^2+, Mg^2+ and Fe^2+ on the binding constant between EGCG and BSA were studied at 298 K. The effect of EGCG on the conformation of BSA was also analyzed by synchronous fluorescence spectroscopy. PACS. 21. 10. Dr; 32. 50. +d; 32. 30. Jc; 82.80. Dx展开更多
Strategies for labeling proteins with fluorophores are always important for biotechnology. Here we take a model protein(bovine serum albumin) and a typical fluorophore(rhodamine B) to demonstrate a direct labeling met...Strategies for labeling proteins with fluorophores are always important for biotechnology. Here we take a model protein(bovine serum albumin) and a typical fluorophore(rhodamine B) to demonstrate a direct labeling method just by physical adsorption. In combination with size exclusion chromatography and the Scartchard equation, we have developed a facile analysis method for calculating the binding constant and binding sites.The molecular docking method has been used to study the binding site in amino acid level.展开更多
基金receiving a fellowship from UGCNew Delhi[University Grant Commission,the XIth plan(Faculty Improvement Programme)]DST and UGC for providing funds to the department under FIST and SAP programme
文摘A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-(4-N, N-dimethylaminophenyl)-pyr- imidine-5-carbonitrile (AHDMAPPC), was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin (BSA) in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites (n ≈ 1) were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change (AH), free energy (AG) and entropy change (AS) for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van't Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster's theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism (CD) and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.
文摘Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.
文摘Hydroxycinnamic acids (HCAs) possess numer- ous biological effects including antioxidant, antiallergic, antimicrobial, and immunomodulatory activities and due to these properties are widely used in folk medicine. Nevertheless, they can interact with protein molecules and cause some structural and functional changes. The possib- ility of HCAs binding to bovine serum albumin (BSA) under physiological conditions was inve- stigated by the UV-VIS absorption spectroscopy and fluorescence quenching method. Apart from rosmarinic acid, all tested HCAs quenched tryptophan fluorescence of BSA in the studied range of concentrations (0-20 μM) mainly by static quenching mechanism (formation of non- fluorescent HCA-BSA complexes). The binding constants, number of binding sites and free energy changes were determined. The binding affinities of HCAs were ranked in the order: chlorogenic acid > sinapic acid ≥ caffeic acid > ferulic acid > o-coumaric acid > p-coumaric acid ≥ m-coumaric acid, which was confirmed by spectral overlaps of BSA emission spectrum with absorption spectrum of HCA. All free energy changes possessed negative sign indicating the spontaneity of HCA-BSA interaction.
文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.
基金Department of Science and Technology(DST,Project no.SR/SO/BB-54/2007),Government of India for financial support
文摘The interaction of baicalein with bovine serum albumin(BSA) was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 10~5 M^(-1) from fluorescence quenching studies.Negative ΔH°(-5.66 + 0.14 kJ/mol) and positive(ΔS°)(+ 79.96 + 0.65J/mol K) indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°.The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate(SDS) due to probable hydrophobic association of baicalein with SDS,resulting in a negative ΔS°(-40.65 + 0.87 J/mol K).Matrix-assisted laser desorption ionization/time of flight(MALDI-TOF) experiments indicate a 1:1 complexation between baicalein and BSA.The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements.It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA.The presence of metal ions(Ag~+,Mg^(2+),Ni^(2+),Mn^(2+),Co^(2+) and Zn^(2+)) increased the binding affinity of ligand towards BSA.The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism(CD) and Fourier transform infrared(FT-IR) spectroscopic techniques.Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1(subdomain MA) of BSA.
文摘The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.
文摘Objective: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). Methods: We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results: Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in I0 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-flee survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). Conclusions: The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
文摘The binding mechanism of the interactions of halide ions (F–, Br– and I–) with bovine serum albumin (BSA) and hemoglobin (Hb) were studied at different temperatures, by using ion-selective electrodes. The experimental data were treated according to Klotz equation, and the number of binding sites and the binding constants were determined. The results show that the binding sites of F– on protein molecules are more than those of Br– and I–. Additionally, the number of the binding sites for halide ions on protein molecules increases with increasing temperature. This study also indicates that the binding constants for the interactions of halide ions with proteins gradually decrease as the size of halide ions and temperature increases. These behaviors were reasonably interpreted with the structural and thermodynamic factors. The thermodynamic functions at different temperatures were calculated with thermodynamic equations, and the enthalpy change for the interactions were also determined by isothermal titration calorimetry (ITC) at 298.15 K, which indicate that the interactions of halide ions with proteins are mainly electrostatic interaction.
文摘The binding of (-)-epigallocatechin-3-O-gallate (EGCG) to bovine serum albumin (BSA) were investigated for the first time with spectral methods, including fluorescence and absorption spectrometry under simulative physiological conditions. A strong fluorescence quenching reaction of EGCG to BSA was observed. It was proved that the fluorescence quenching of BSA by addition of EGCG was a result of the formation of EGCG-BSA complex. The binding constant K and the number of binding sites n were determined at physiological conditions and three different temperatures with fluorescence quenching method. The binding distance R and transfer efficiency E between BSA and EGCG were also obtained according to Forster theory of non-radiation energy transfer. The effects of Al^3+, Cu^2+, Mg^2+ and Fe^2+ on the binding constant between EGCG and BSA were studied at 298 K. The effect of EGCG on the conformation of BSA was also analyzed by synchronous fluorescence spectroscopy. PACS. 21. 10. Dr; 32. 50. +d; 32. 30. Jc; 82.80. Dx
基金Supported by the National Natural Science Foundation of China(Nos.21171086 and 81160213)Inner Mongolia Autonomous Region science and Technology Department(No.211-202077)+2 种基金Inner Mongolia Grassland Talent(No.108-108038)Natural Science Foundation of Inner Mongolia Autonomous Region of China(No.2013MS1121)Inner Mongolia Agricultural University(Nos.109-108040,211-109003 and 211-206038)
文摘Strategies for labeling proteins with fluorophores are always important for biotechnology. Here we take a model protein(bovine serum albumin) and a typical fluorophore(rhodamine B) to demonstrate a direct labeling method just by physical adsorption. In combination with size exclusion chromatography and the Scartchard equation, we have developed a facile analysis method for calculating the binding constant and binding sites.The molecular docking method has been used to study the binding site in amino acid level.