Recently microwave-induced chemical synthesis of curcumin-metformin adduct to enhance the efficacy of metformin in preventing the formation of Advanced Glycation End Products （AGEs） has been reported from authors＇ ...Recently microwave-induced chemical synthesis of curcumin-metformin adduct to enhance the efficacy of metformin in preventing the formation of Advanced Glycation End Products （AGEs） has been reported from authors＇ laboratory. The present studies describe microwave-induced chemical synthesis and mass spectral characterization of curcumin-phenformin adducts using LC-MS/MS. The mechanism of formation and its analytical data via Thin-Layer Chromatography （TLC） combined with MS/MS fragmentation revealed a major six membered ring adduct and a minor eight membered ring isomer. A facile chemical synthesis and identification of major and minor isomers presented in this study may offer novel therapeutic strategies for inhibiting AGEs as well as anti-cancer treatments.展开更多
SalNa （sodium salinomycin） reacts with divalent transition metal ions of Co（II）, Ni（II）, Cu（II） and Zn（II） to produce novel compounds characterized by various spectroscopic methods. The interaction of metal ...SalNa （sodium salinomycin） reacts with divalent transition metal ions of Co（II）, Ni（II）, Cu（II） and Zn（II） to produce novel compounds characterized by various spectroscopic methods. The interaction of metal （II） ions with SalNa results in the formation of mononuclear complexes of a general composition of [M（Sal）2·（H2O）2] nH2O （n = 0 or 2） where the divalent cations replace Na~ ions from the cavity of initial compound. The new compounds （disalinomycinates） possess an enhanced antibacterial activity against Gram-positive microorganisms as compared to both SalNa and SalH （salinomycinic acid）, respectively. The metal （II） complexes manifest strong concentration dependent cytotoxic effect in experiments using human leukemia cell lines. The complexes of Co0I） and Cu（lI） proved to exert superior activity as compared to the Ni（II） and Zn（II） analogues and are much more cytotoxic than SalNa and SalH. Further studies should be conducted to determine the therapeutic indexes of the new compounds.展开更多
Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than w...Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.展开更多
Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serio...Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serious cardio-cytotoxic effects. The aim of this study was to investigate the effect of neferine, a bisbenzylisoquinoline alkaloid extracted from the green embryo in the mature lotus seed, on the pharmacokinetics of doxorubicin. The levels of doxorubicin in plasma and tissues were measured using the high performance liquid chromatography（HPLC） method. The chromatographic separation was completed on a reversed-phase C18 column using acetonitrile–phosphate buffer（30：70, v/v） as the mobile phase at a flow rate of 1 mL /min and ultraviolet detection wave length was set at 233 nm. The pharmacokinetic study found that the co-administration of neferine and doxorubicin significantly affected the pharmacokinetics of doxorubicin. There were evident changes in area under the curve（AUC）, clearance（CL） and t1/2β in group of pretreatment neferine as compared with those in group treated with doxorubicin alone. Tissue distribution analysis showed that the concentrations of doxorubicin distributed to heart, liver and kidney were statistically significant higher in group of pretreatment with neferine plus doxorubicin than those in the doxorubicin alone-group at 0.5 h and 2 h after drug administration, respectively. While the doxorubicin concentrations in spleen and lung drug were slightly increased in the group of pretreatment with neferine plus doxorubicin as compared to that of group of doxorubicin alone, the difference between two groups were not statistically significant. Therefore, the dose of doxorubicin needs to be taken into consideration when it is administrated in combination with neferine.展开更多
文摘Recently microwave-induced chemical synthesis of curcumin-metformin adduct to enhance the efficacy of metformin in preventing the formation of Advanced Glycation End Products （AGEs） has been reported from authors＇ laboratory. The present studies describe microwave-induced chemical synthesis and mass spectral characterization of curcumin-phenformin adducts using LC-MS/MS. The mechanism of formation and its analytical data via Thin-Layer Chromatography （TLC） combined with MS/MS fragmentation revealed a major six membered ring adduct and a minor eight membered ring isomer. A facile chemical synthesis and identification of major and minor isomers presented in this study may offer novel therapeutic strategies for inhibiting AGEs as well as anti-cancer treatments.
文摘SalNa （sodium salinomycin） reacts with divalent transition metal ions of Co（II）, Ni（II）, Cu（II） and Zn（II） to produce novel compounds characterized by various spectroscopic methods. The interaction of metal （II） ions with SalNa results in the formation of mononuclear complexes of a general composition of [M（Sal）2·（H2O）2] nH2O （n = 0 or 2） where the divalent cations replace Na~ ions from the cavity of initial compound. The new compounds （disalinomycinates） possess an enhanced antibacterial activity against Gram-positive microorganisms as compared to both SalNa and SalH （salinomycinic acid）, respectively. The metal （II） complexes manifest strong concentration dependent cytotoxic effect in experiments using human leukemia cell lines. The complexes of Co0I） and Cu（lI） proved to exert superior activity as compared to the Ni（II） and Zn（II） analogues and are much more cytotoxic than SalNa and SalH. Further studies should be conducted to determine the therapeutic indexes of the new compounds.
文摘Objective： Our group has previously observed that in patients with small-cell lung cancers （SCLCs）, the expression of a tumor antigen, glioma big potassium （gBK） ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein （TAPP）. We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods： SCLC samples （eight surgical resections and three autopsy samples） and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results： Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of PS3-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion： Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.
基金The Scientific Research Fund Project of Heilongjiang University of Chinese Medicine(Grant No.201420)
文摘Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serious cardio-cytotoxic effects. The aim of this study was to investigate the effect of neferine, a bisbenzylisoquinoline alkaloid extracted from the green embryo in the mature lotus seed, on the pharmacokinetics of doxorubicin. The levels of doxorubicin in plasma and tissues were measured using the high performance liquid chromatography（HPLC） method. The chromatographic separation was completed on a reversed-phase C18 column using acetonitrile–phosphate buffer（30：70, v/v） as the mobile phase at a flow rate of 1 mL /min and ultraviolet detection wave length was set at 233 nm. The pharmacokinetic study found that the co-administration of neferine and doxorubicin significantly affected the pharmacokinetics of doxorubicin. There were evident changes in area under the curve（AUC）, clearance（CL） and t1/2β in group of pretreatment neferine as compared with those in group treated with doxorubicin alone. Tissue distribution analysis showed that the concentrations of doxorubicin distributed to heart, liver and kidney were statistically significant higher in group of pretreatment with neferine plus doxorubicin than those in the doxorubicin alone-group at 0.5 h and 2 h after drug administration, respectively. While the doxorubicin concentrations in spleen and lung drug were slightly increased in the group of pretreatment with neferine plus doxorubicin as compared to that of group of doxorubicin alone, the difference between two groups were not statistically significant. Therefore, the dose of doxorubicin needs to be taken into consideration when it is administrated in combination with neferine.
