不可逆电活性药物米托蒽醌与脱氧核糖核酸的相互作用

研究了抗癌新药米托蒽醌(MXT)的电化学行为及与脱氧核糖核酸(DNA)的相互作用，推导了适用于研究不可逆电活性分子与DNA相互作用的电化学公式，运用该公式可以简便、快速地测定靶向分子与DNA的结合常数和结合位点数。实验发现，MXT与小牛胸腺DNA的结合以蒽醌母核的嵌插作用为主，同时，烃氨基侧链与骨架磷酸基团之间的静电吸引对母核起稳定作用，使化合物易于嵌入DNA的平面结构。MXT与DNA相互作用引起的峰电流的变化可以用于分析测定DNA。     

米托蒽醌与B-DNA相互作用的分子模拟

针对嵌插型抗癌药物米托蒽醌(mitoxantrone,MTX)同B-DNA间作用模式的争议,采用分子模拟方法研究了米托蒽醌分子与B-DNA分子的相互作用.结果表明:米托蒽醌分子插入到B-DNA中有大小沟选择性及碱基对特异性,更倾向从小沟方向插入到DNA分子中;对5'-CG碱基对有特异性识别.通过详细能量项的分析,揭示了米托蒽醌插入DNA分子的驱动力及对碱基的特异性识别作用主要是空间相互作用特别是静电相互作用.在最佳作用位点复合物的构象分析则表明蒽醌环只有一部分插入碱基对中,侧链在小沟中延磷酸基骨架以3'-5'方向伸展,并通过静电作用进一步增强米托蒽醌与B-DNA的结合.     

Novel green synthesis of Boswellia serrata leaf aqueous extract conjugated gold nanoparticles with excellent anti-acute myeloid leukemia property in comparison to mitoxantrone in a leukemic mice model: Introducing a new chemotherapeutic drug

The present research confirms the capacity of aqueous extract of Boswellia serrata grown under in vitro condition for the green synthesis of gold nanoparticles (AuNPs). Also, we showed the cytotoxicity, antioxidant, and anti-acute myeloid leukemia properties of AuNPs compared to mitoxantrone in a leukemic mouse model. The synthesized AuNPs were characterized using several techniques including XRD, TEM, FE-SEM, UV–Vis, and FT-IR. From the XRD pattern, four distinct diffraction peaks at 38.2°, 44.2°, 64.7° and 77.4° are indexed as (111), (200), (220) and (311) planes of FCC metallic gold. TEM and FE-SEM images revealed an average diameters of 15–30 nm for the nanoparticles. FT-IR findings offered antioxidant compounds in the nanoparticles were the sources of reducing power, reducing gold ions to AuNPs. UV–Vis revealed an absorption band at 536 nm that is related to the surface plasmon resonance of AuNPs. In vivo design, induction of acute myeloid leukemia was done by DMBA in 75 mice. Then, the mice were randomly divided into six subgroups, including untreated, control, HAuCl₄, B. serrata, AuNPs, and mitoxantrone. AuNPs (In the dose of 1 mg/kg body weight) similar to mitoxantrone, significantly (p ≤ 0.05) increased the platelet, lymphocyte, and RBC parameters and the anti-inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and reduced the weights and volumes of liver and spleen and their sub-compartment, the total WBC, blast, monocyte, neutrophil, eosinophil, and basophil counts, and the pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα) as compared to the untreated mice. By quantitative Real-Time PCR, S1PR1 and S1PR5 mRNA expression in lymphocytes were significantly (p ≤ 0.05) increased by treating the leukemic mice with the AuNPs and mitoxantrone. In vitro design, AuNPs similar to mitoxantrone had low cell viability dose-dependently against Human HL-60/vcr, 32D-FLT3-ITD, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. Besides, the DPPH assay showed similar antioxidant potentials for AuNPs and mitoxantrone. In conclusion, the results of this research indicated the excellent capacity of synthesized gold nanoparticles using B. serrata leaf aqueous extract in the treatment of acute myeloid leukemia in leukemic mice.     

Enhanced Efficiency of the Removal of Cytostatic Anthracycline Drugs Using Immobilized Mycelium of Bjerkandera adusta CCBAS 930

The aim of this study was to evaluate the bioremoval of anthracycline antibiotics (daunomycin-DNR, doxorubicin–DOX, and mitoxantrone-MTX) by immobilized mycelium of B. adusta CCBAS 930. The activity of oxidoreductases: versatile peroxidases (VP), superoxide dismutase (SOD), catalase (CAT), and glucose oxidase (GOX), and the levels of phenolic compounds (PhC) and free radicals (SOR) were determined during the biotransformation of anthracyclines by B. adusta strain CCBAS 930. Moreover, the phytotoxicity (Lepidium sativum L.), biotoxicity (MARA assay), and genotoxicity of anthracyclines were evaluated after biological treatment. After 120 h, more than 90% of anthracyclines were removed by the immobilized mycelium of B. adusta CCBAS 930. The effective biotransformation of anthracyclines was correlated with detoxification and reduced genotoxicity.     

Determination of mitoxantrone with a fiber-optic device

A major problem in therapeutic use of the cytostatic agent mitoxantrone is the occurrence of side effects. Estimation of the drug concentration in or next to the tumor can lead to a reduction of the toxicity through accurate dose adjustment. In this paper a method for the determination of mitoxantrone by a fibre-optic device is described. The advantage of the system is the possibility of remote sensing at the working site of the cytostatic agent by a method that is simple in handling and sufficient in sensitivity. The measuring principle is based on the blue colour of mitoxantrone. The function of the device was tested byin vitro assays; linear calibration curves in a concentration range between 2 and 10g of mitoxantrone per ml of sample solution were obtained.     

Green formulation and chemical characterization of Lens culinaris seed aqueous extract conjugated gold nanoparticles for the treatment of acute myeloid leukemia in comparison to mitoxantrone in a leukemic mouse model

The high prevalence of cancer has been increased the rate of studying about the new formulation of chemotherapeutic drugs. In this regards, one of the suitable options is the use of metal nanoparticles for formulating these drugs. In the recent study, Lens culinaris seed aqueous extract conjugated gold nanoparticles (AuNPs) are reported for the first time to exert a dietary therapeutic potential compared to mitoxantrone in an animal model of acute myeloid leukemia. The synthesized AuNPs were characterized using different techniques including UV–Vis., FT-IR, XRD, FE-SEM, and TEM. DPPH free radical scavenging test was done to evaluate the antioxidant potentials of HAuCl₄, L. culinaris, AuNPs, and mitoxantrone. For the analyzing of cytotoxicity effects of HAuCl₄, L. culinaris, AuNPs, and mitoxantrone, MTT assay was used on HUVEC, 32D-FLT3-ITD, Human HL-60/vcr, and Murine C1498 cell lines. In vivo assay, induction of acute myeloid leukemia was done by 7,12-Dimethylbenz[a]anthracene (DMBA) in 75 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, HAuCl₄, L. culinaris, AuNPs, and mitoxantrone. SEM and TEM images showed uniform spherical morphology and average diameters of 10–40 nm for the nanoparticles. DPPH test revealed similar antioxidant potentials for mitoxantrone and AuNPs. Similar to mitoxantrone, AuNPs had low cell viability dose-dependently against 32D-FLT3-ITD, Human HL-60/vcr, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. AuNPs and mitoxantrone significantly (p ≤ 0.05) reduced the weight and volume of liver and spleen, the pro-inflammatory cytokines, and the total WBC, blast, neutrophil, monocyte, eosinophil, and basophil counts and increased the mRNA expression of Sphingosine-1-phosphate receptor-1 and Sphingosine-1-phosphate receptor-5, the anti-inflammatory cytokines, and the lymphocyte, platelet, and RBC parameters as compared to the untreated mice. It looks that AuNPs can be administrated as a chemotherapeutic supplement or drug for the treatment of acute myeloid leukemia in the clinical trial.     

Preparation,formulation, and chemical characterization of silver nanoparticles using Melissa officinalis leaf aqueous extract for the treatment of acute myeloid leukemia in vitro and in vivo conditions

The demand for nanoparticles is increasing day by day due to their wide range of applications in various areas including pharmaceutical industry. Nanoparticles are formally synthesized by chemical methods in which the toxic and flammable chemicals are used. Synthesis of nanoparticles from various biological systems has been reported, but among all, biosynthesis of nanoparticles from plants is considered as the most suitable method. The current study confirms the potential of aqueous extract of Melissa officinalis grown under in vitro condition for the green synthesis of silver nanoparticles (AgNPs). Also, we revealed the cytotoxicity, antioxidant, and anti-acute myeloid leukemia effects of AgNPs compared to mitoxantrone in a leukemic mouse model. The synthesized AgNPs were characterized using several techniques including UV–Vis., FT-IR, TEM, FE-SEM, and EDS. In vivo experiment, induction of acute myeloid leukemia was done by DMBA in 75 mice. The obtained results were fed into SPSS-22 software and analyzed by one-way ANOVA. By quantitative real-time PCR, S1PR1 and S1PR5 mRNA expression in lymphocytes were significantly (p ≤ 0.01) increased by treating the leukemic mice with the AgNPs and mitoxantrone. Also, AgNPs similar to mitoxantrone, significantly (p ≤ 0.01) enhanced the platelet, lymphocyte, and RBC parameters and the anti-inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and reduced the total WBC, blast, monocyte, neutrophil, eosinophil, and basophil counts and the pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα) as compared to the untreated mice. In vitro experiment, AgNPs similar to mitoxantrone had low cell viability dose-dependently against murine C1498, human HL-60/vcr, and 32D-FLT3-ITD cell lines without any cytotoxicity on HUVEC cell line. Furthermore, the DPPH assay showed similar antioxidant potentials for AgNPs and mitoxantrone. Above results approve the excellent anti-acute myeloid leukemia, cytotoxicity, and antioxidant properties of AgNPs compared to mitoxantrone.     

Validated Assay for the Determination of Mitoxantrone in Pharmaceuticals Using Capillary Zone Electrophoresis

Abstract

The first capillary zone electrophoretic (CZE) method for the determination of mitoxantrone (MTX) in pharmaceutical formulations was developed. The influence of background electrolyte (BGE) species, pH, concentration (c _BGE), organic modifier, capillary temperature, applied voltage, and injection time was investigated. Optimum results were achieved with 25 mM ammonium acetate at an apparent pH value of 5.0 in 50% v/v acetonitrile, applied voltage of +30 kV, and capillary temperature of 25°C. The samples were introduced into the capillary hydrodynamically for 2 s at 33.5 mbar. Mitoxantrone was detected at a wavelength of 242 nm. Mitoxantrone and doxorubicin (DOX) (used as internal standard, ISTD) were completely separated in less than 7 min. The method was suitably validated with respect to linearity, limits of detection (LOD) and quantification (LOQ), accuracy, precision, selectivity, and robustness. The proposed method was applied successfully for the determination of MTX in its injectable pharmaceutical formulation.     

米托蒽醌在金电极上的电化学研究及其应用

米托蒽醌(MTX)在0.2 mol/L B-R缓冲溶液(pH=1.5)中循环伏安扫描时,在金电极上会产生一个灵敏的氧化峰P1(峰电位为1.087 V)和两个灵敏的还原峰P2(峰电位为0.817 V)、P3(峰电位为0.764 V)。P1峰电流值与MTX浓度在1.0×10-9~1.0×10-6mol/L范围内呈良好的线性关系;其检出限可达5.6×10-10mol/L。本研究优化了测定米托蒽醌的最佳实验条件,建立了可灵敏测定米托蒽醌的新方法;同时对米托蒽醌在金电极上的电化学行为进行了较为详细的研究。     

Chemiluminescence method for the determination of mitoxantrone by the enhancement of the tris-(4,7-diphenyl-1,10-phenanthrolinedisulfonic acid)ruthenium(II)–cerium(IV) system

2,5-Dimercapto-1,3,4-thiadiazole (DMTD) self-assembled monolayer on gold electrode was prepared and investigated by electrochemical measurement. The DMTD/Au electrode exhibited a significantly increased sensitivity and selectivity for Pb(II) in acetate buffer (pH 5.5) at a potential of −1.0 V (vs Ag/AgCl) for 4 min by anodic stripping voltammetry. The influence of various experimental parameters on the voltammetric response was studied. Under the optimized working conditions, the dependence of the stripping peak current response on concentration of Pb(II) was linear in the range of 1–45 μmol L⁻¹ with a correlation coefficient of 0.9988, and the detection limit was 0.10 μmol L⁻¹. The relative standard deviation of the results was 3.4% for six successive determinations of a 20 μmol L⁻¹ Pb(II) solution. A study of interfering substances was also performed. The method was applied to the determination of Pb(II) in water samples with satisfactory results. Correspondence: Hong Qun Luo, School of Chemistry and Chemical Engineering, Southwest University, 400715 Chongqing, China