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COMPLEX-FORMING PROPERTIES OF SYNTHETIC PYRIMIDINONE NUCLEOSIDES WITH Ag(I) IONS IN AN AQUEOUS SOLUTION 水溶液中合成嘧啶酮核苷与Ag(I)离子的络合性质
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-04-28 DOI: 10.32383/appdr/162766
M. Pająk, M. Woźniczka, M. Świątek, Bartłomiej Czerwiński, J. Włodarczyk, J. Fichna
The present work describes the complexation properties of two synthetic nucleosides (used as ligands), i.e. β-D-ribofuranoside-4-pyrimidinone (ribo) and β-D-deoxyribofuranoside-4-pyrimidinone (deoxy) with Ag(I) ions in aqueous solution. The stability constants of the studied coordination entities were calculated potentiometrically. The logarithm values of the overall stability constants of the coordination entities were found to be [Ag-deoxy]+ = 3.07, [Ag-(deoxy)2]+ = 6.90, [Ag-ribo]+ = 3.00 and [Ag-(ribo)2]+ = 6.63. Based on the species distribution curves as a function of CL/CM, the percentage of each coordination entity formed in aqueous solution was estimated (12 % [Ag-deoxy]+; 36 % [Ag-(deoxy)2]+; 16 % [Ag-ribo]+; 26 % [Ag-(ribo)2]+). It was found that the ligands form coordination entities with Ag(I) ions with stoichiometric ratios M : L = 1 : 1 and 1 : 2. Such coordination entities may show potential antiviral, antibacterial, and antitumor properties, which warrants further in vitro and in vivo studies. They may also be of great interest for their application in nanobiotechnology.
本工作描述了两种合成核苷(用作配体),即β-D-呋喃核糖-4-嘧啶酮(核糖)和β-D-脱氧呋喃核糖-4-吡啶酮(脱氧)在水溶液中与Ag(i)离子的络合性质。用电位法计算了所研究的配位体的稳定常数。发现配位实体的总稳定性常数的对数值为[Ag-脱氧]+=3.07,[Ag-(脱氧)2]+=6.90,[Ag核糖]+=3.00和[Ag-核糖2]+=6.63。基于作为CL/CM函数的物种分布曲线,估计了在水溶液中形成的每个配位实体的百分比(12%[Ag-脱氧]+;36%[Ag-(脱氧)2]+;16%[Ag-rib]+;26%[Ag-(核糖)2]+)。发现配体与化学计量比M∶L=1∶1和1∶2的Ag(I)离子形成配位体。这种配位实体可能表现出潜在的抗病毒、抗菌和抗肿瘤特性,这需要进一步的体外和体内研究。它们在纳米生物技术中的应用也可能引起人们的极大兴趣。
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引用次数: 0
A combination of simvastatin and low-protein diet increases renal 2-oxoglutarate dehydrogenase activity in rats 辛伐他汀和低蛋白饮食联合使用可增加大鼠肾脏2-氧戊二酸脱氢酶活性
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/159789
Małgorzata Belczyk, M. Knapik-Czajka, A. Gawedzka, K. Mikołajczyk, J. Drag
Mitochondrial 2-oxoglutarate dehydrogenase complex (2-OGDH) that consists of multiple copies of 3 catalytic subunits (E1, E2, E3) is a regulatory enzyme of tricarboxylic acid cycle. 2-OGDH together with branched chain α-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) belongs to the 2-oxoacid dehydrogenases family. It was shown that in protein-restricted rats simvastatin stimulated liver BCKDH, whereas it exerted no effect on BCKDH in rats fed a standard diet. We hypothesized that combination of simvastatin and low-protein diet could have an impact on renal 2-OGDH. The purpose of the study was to determine the effect of combination of simvastatin and low-protein diet on renal 2-OGDH in rats. Simvastatin (80 mg/kg b.wt/day) or the vehicle (0.3% methylcellulose) were administered orally (for 14 days) to rats fed low-protein (8% protein) or standard (23% protein) diet. 2-OGDH activity, protein levels and mRNA levels for E1 and E2 subunits were determined. In addition, serum creatinine level was measured. Results: The combination of simvastatin and low-protein diet elicited the increase of renal 2-OGDH activity that corresponded to the increase of E1 protein, but not of E1 mRNA level. In contrast, simvastatin treatment did not affect 2-OGDH activity, nor protein and mRNA levels of E1 in rats fed standard diet. Serum creatinine levels were not changed upon simvastatin administration in any group. In conclusion, the results of present study indicate that combination of simvastatin and low-protein diet induces stimulation of renal 2-OGDH complex probably at post-transcriptional level.
线粒体2-氧戊二酸脱氢酶复合体(2-OGDH)由3个催化亚基(E1, E2, E3)的多个拷贝组成,是三羧酸循环的调节酶。2-OGDH与支链α-酮酸脱氢酶(BCKDH)和丙酮酸脱氢酶(PDH)一起属于2-氧酸脱氢酶家族。研究表明,在蛋白质受限的大鼠中,辛伐他汀刺激了肝脏BCKDH,而在喂食标准饮食的大鼠中,辛伐他汀对BCKDH没有影响。我们假设辛伐他汀联合低蛋白饮食可能对肾脏2-OGDH有影响。本研究旨在探讨辛伐他汀联合低蛋白饮食对大鼠肾脏2-OGDH的影响。将辛伐他汀(80mg /kg b.w.t /天)或对照物(0.3%甲基纤维素)口服给喂食低蛋白(8%蛋白质)或标准(23%蛋白质)饮食的大鼠(14天)。测定2-OGDH活性、E1和E2亚基蛋白水平和mRNA水平。同时测定血清肌酐水平。结果:辛伐他汀联合低蛋白饮食可引起肾脏2-OGDH活性升高,与E1蛋白升高相对应,但与E1 mRNA水平升高不一致。相比之下,辛伐他汀治疗不影响标准饮食大鼠的2-OGDH活性,也不影响E1的蛋白质和mRNA水平。服用辛伐他汀后,各组血清肌酐水平均未发生变化。综上所述,本研究结果提示,辛伐他汀联合低蛋白饮食可能在转录后水平诱导肾脏2-OGDH复合物的刺激。
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引用次数: 0
Quantitative chirality in the binding of androgens to their receptor 雄激素与其受体结合的定量手性
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/161082
Piotr F. J. Lipiński, J. Dobrowolski, A. Baraniak
Chirality is a binary yes/no molecular property that nevertheless can be described by a continuous chirality measure function. Chirality measure values can be understood as sensitive descriptors of molecular shape. In this study, we evaluated the role of quantitative chirality (measures) in binding of androgens to their receptor. We demonstrate that a simple Quantitative Structure-Activity Relationship equation correlating the binding affinity with the partial charges of pharmacophoric oxygen atoms is significantly improved upon introducing quantitative chirality descriptors as additional variables. In such models, the charge descriptors account for the strength of the formed hydrogen bonds. However, the picture is completed by the chirality measures that indirectly contain information on the geometries of the hydrogen bond networks and subtle differences in the van der Waals contacts connected with different local or global shapes of the molecules. The model case studied here (11 simple and very similar steroids) proves that both global and local chirality is important in the androgen binding to their receptors.
手性是二元的是/否分子性质,但可以用连续的手性测度函数来描述。手性测量值可以理解为分子形状的敏感描述符。在这项研究中,我们评估了定量手性(测量)在雄激素与其受体结合中的作用。我们证明,在引入定量手性描述符作为附加变量后,将结合亲和力与药效氧原子的部分电荷相关联的简单定量构效关系方程得到了显著改进。在这样的模型中,电荷描述符解释了形成的氢键的强度。然而,手性测量间接包含了氢键网络的几何信息,以及与分子的不同局部或整体形状相连的范德瓦尔斯接触的细微差异,从而完成了这幅图景。本文研究的模型案例(11种简单且非常相似的类固醇)证明,在雄激素与其受体结合的过程中,全局和局部手性都很重要。
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引用次数: 0
Validated HPLC-UV method for determination of venlafaxine and its metabolite - o-desmethylvenlafaxine in human plasma HPLC-UV法测定人血浆中文拉法辛及其代谢产物邻去甲基文拉法辛的含量
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/159659
T. Pawiński, I. Szlaska, Monika Kukiełka, Kinga Kośnik
This paper describes a simple, rapid and cost-effective HPLC-UV method for the determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma. Sample preparation is based on a liquid-liquid extraction procedure with a short extraction time. Prazosine hydrochloride was used as the internal standard. The HPLC separation was performed on a Supelcosil LC-CN column, using a mobile phase consisting acetonitrile : 25 mM phosphate buffer at pH 3,5 (15:85 v/v). The calibration curve is linear in the concentrations range of 25-1000 ng/mL, which is suitable for pharmacokinetic studies of venlafaxine hydrochloride following of dosing from 37.5 mg to 375.0 mg per day. The method was fully validated according to the international guidances,
本文介绍了一种简单、快速、经济高效的HPLC-UV法测定人血浆中文拉法辛及其活性代谢产物O-去甲基文拉法辛的含量。样品制备基于液-液萃取程序,萃取时间短。以盐酸普唑嗪为内标。HPLC分离在Supelcosil LC-CN柱上进行,使用由乙腈:25mM磷酸盐缓冲液组成的流动相,pH为3,5(15:85v/v)。在25-1000 ng/mL的浓度范围内,校准曲线是线性的,这适用于每天37.5 mg至375.0 mg给药后盐酸文拉法辛的药代动力学研究。该方法根据国际指南进行了充分验证,
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引用次数: 0
Acetylcholinesterase inhibitors:  structure-activity relationship and kinetic studies on selected flavonoids 乙酰胆碱酯酶抑制剂:部分黄酮类化合物的构效关系及动力学研究
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/159798
K. Jakimiuk, Diana Nazaruk, M. Tomczyk
Flavonoids are secondary plant metabolites that have long been included in the human diet. These natural products are well known for their beneficial effects on health. Thus, in this study, the in vitro inhibitory activity of 28 different flavonoids (1-28) against acetylcholinesterase was evaluated, and the type of inhibition for the most active compound (12) was studied. Acetylcholinesterase (AChE) inhibitors are considered the main class of medication used for the treatment of the primary dementia phase in Alzheimer's disease (AD). Our study used galantamine as a positive control and showed that 7,8-dihydroxyflavone (12) has the highest anti-acetylcholinesterase activity. The inhibitory type of 7,8-dihydroxyflavone, which is non-competitive inhibition, was determined for the first time. Furthermore, the obtained data allowed us to identify the characteristic flavonoid structure that facilitates AChE inhibition: the presence of a hydroxyl group at C7 in the benzo-γ-pyrane ring of the molecule.
黄酮类化合物是植物次生代谢物,长期以来一直包含在人类饮食中。众所周知,这些天然产品对健康有益。因此,本研究对28种黄酮类化合物(1-28)对乙酰胆碱酯酶的体外抑制活性进行了评价,并对活性最高的化合物(12)的抑制类型进行了研究。乙酰胆碱酯酶(AChE)抑制剂被认为是用于治疗阿尔茨海默病(AD)原发性痴呆期的主要药物。我们的研究以加兰他敏作为阳性对照,结果表明7,8-二羟黄酮(12)具有最高的抗乙酰胆碱酯酶活性。首次确定了7,8-二羟黄酮的抑制类型为非竞争性抑制。此外,获得的数据使我们能够确定促进AChE抑制的黄酮类化合物的特征结构:在分子的苯并-γ-pyrane环的C7处存在羟基。
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引用次数: 1
Study of glycopyrrolate dry powder behavior in new single dose inhalers under generic product development 仿制产品开发中新型单剂量吸入器中甘罗酸干粉行为的研究
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/160204
Jakub Strzemieczny, Bogusława Musiał, Agnieszka Pawlaczyk, M. Sznitowska, D. Siluk
With increasing environmental pollution and tendency to smoking, the number of patients suffering from chronic obstructive pulmonary disease is increasing and a demand for generic products for the treatment of chronic obstructive pulmonary disease (COPD) is growing. The long process of generic formulation development can be accelerated by using an inhaler with suitable fluid dynamics features. This paper presents a study of a newly patented single-dose Memmatec Mora® inhaler in two versions: with grid openings 1.0 (A) and 0.5 mm (B), using Seebri Breezhaler® as a reference product. The studies were conducted with inhalation powders containing 44μg glycopyrronium bromide placed in a capsule. The manuscript presents studies during the selection of a generic inhaler within the course of inhalation powder development by a pharmaceutical company. The fluid dynamics features of the inhalers and the dose delivered were determined. The aerodynamic particle size distribution (APSD) and the inhalable dose were tested using a cascade impactor. The delivery dose for the Breezhaler, Mora A and Mora B inhalers for a volumetric flow of 100 L×min-1 was 38.5, 40.5 40.3μg, respectively. Fine particle fraction of the inhalers tested was 22.3, 24.6 25.5μg, respectively. Results of the study indicate that increase of the glycopyrronium bromide inhalation dose can be achieved not only by changes in the manufacturing technology of inhalation powder, hard capsule technology or addition of best quality raw materials, but also by the use of a properly selected inhaler with specific fluid dynamics features.
随着环境污染的加剧和吸烟的趋势,慢性阻塞性肺疾病患者的数量不断增加,对慢性阻塞性肺疾病(COPD)治疗的仿制产品的需求不断增长。通过使用具有适当流体动力学特性的吸入器,可以加快仿制制剂开发的漫长过程。本文介绍了一种新专利的单剂量Memmatec Mora®吸入器的研究,该吸入器有两个版本:栅格开口1.0 (a)和0.5 mm (B),使用Seebri Breezhaler®作为参考产品。研究人员将含有44μg甘溴铵的吸入粉末放入胶囊中。手稿提出了研究期间的选择一个通用吸入器在吸入粉末开发过程中由制药公司。确定了吸入器的流体动力学特性和所给剂量。采用叶栅冲击器测试了空气动力学粒径分布(APSD)和可吸入剂量。在体积流量为100 L×min-1时,Breezhaler、Mora和Mora B吸入器的给药剂量分别为38.5、40.5、40.3μg。吸入器细颗粒物含量分别为22.3、24.6、25.5μg。研究结果表明,增加甘溴铵吸入剂量不仅可以通过改变吸入粉的制造工艺、硬胶囊技术或添加最优质的原料来实现,还可以通过选择适当的具有特定流体动力学特性的吸入器来实现。
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引用次数: 0
Optimization of chromatographic systems for detection and determination of carbamazepine in pharmaceutical formulations, serum, and saliva by HPLC-DAD HPLC-DAD法检测和测定制剂、血清和唾液中卡马西平的色谱系统优化
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/161081
K. Wróblewski, I. Dybała, A. Petruczynik, M. Szultka-Młyńska, Daria Janiszewska, J. Rog, H. Karakuła-Juchnowicz, D. Juchnowicz, B. Buszewski
Carbamazepine (CBZ) is an anticonvulsant drug, widely used also in various disorders like neuropathic pain, bipolar affective disorder, resistant schizophrenia, and trigeminal neuralgia. Appropriate analytical procedures are necessary to monitor, detect and quantify CBZ in pharmaceutical formulations and biological samples. The search for new methods for drug determination is one of the most important challenges of modern scientific research. It is important to study the chromatographic conditions of CBZ analysis, which is necessary for the further development of efficient drug determination methods. In this work, retention, peak symmetry, and system efficiency of CBZ on Polar RP and Phenyl-Hexyl stationary phases were investigated. Various mobile phases containing methanol (MeOH) and/or acetonitrile (ACN) as organic modifiers, acetate buffer, and the addition of diethylamine (DEA) were applied. Different chromatographic systems were compared to obtain satisfying retention, peak shape, and system efficiency. The most optimal chromatographic system with Polar RP column was applied for the determination of CBZ in pharmaceutical formulations, human serum, and saliva by the high-performance liquid chromatography with diode array detection (HPLC-DAD) method. Solid-phase extraction (SPE) method was applied for sample preparation prior to chromatographic analysis. The proposed method was validated for linearity, selectivity, precision, and accuracy. Confirmation of the presence of CBZ and its main metabolites in biological samples obtained from patients was performed using the ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method.
卡马西平(CBZ)是一种抗惊厥药物,也广泛用于各种疾病,如神经性疼痛、双相情感障碍、顽固性精神分裂症和三叉神经痛。适当的分析程序对于监测、检测和量化药物制剂和生物样品中的CBZ是必要的。寻找新的药物测定方法是现代科学研究中最重要的挑战之一。研究CBZ分析的色谱条件具有重要意义,这对于进一步开发有效的药物测定方法是必要的。本文研究了CBZ在极性RP和苯基己基固定相上的保留率、峰对称性和系统效率。应用了以甲醇(MeOH)和/或乙腈(ACN)为有机改性剂、乙酸缓冲液和二乙胺(DEA)的各种流动相。对不同的色谱系统进行了比较,以获得令人满意的保留率、峰形状和系统效率。采用高效液相色谱-二极管阵列检测(HPLC-DAD)法,采用极性RP柱的最佳色谱体系测定了制剂、人血清和唾液中的CBZ。色谱分析前样品制备采用固相萃取法。所提出的方法在线性、选择性、精密度和准确性方面得到了验证。使用超高效液相色谱-串联质谱法(UHPLC-MS/MS)确认从患者获得的生物样品中CBZ及其主要代谢物的存在。
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引用次数: 0
Preparation and characterization of fast-release oral film formulation containing ondansetron hydrochloride solid dispersion 含盐酸昂丹司琼固体分散体口服快释薄膜制剂的制备与表征
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/161039
Ting Wei, Zhongxi Zhao, Ya Zhao
Ondansetron has been widely applied as an antiemetic drug in the treatment or prevention of nausea and vomiting caused by emetic cancer chemotherapy . Fast-release films have the advantages of rapid drug release and improved patients’compliance, especially for the disabled bedridden, the elderly or pediatric patients.The basic film-forming materials were studied through single factor tests and the crystal inhibitors were optimized using solid dispersion technique. The ratio of drug and polymers were optimized by X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) which revealed there was no presence of crystal in the optimized solid dispersion. The final film was white thin films and was smooth in surface without obvious bubbles or cracks. Mean weight of each film was 40~50mg. Mean thichness was 60~70μm. Surface pH was 6.4~6.6. The films could release 85% of drug with 1.5min in 0.1mol/L HCl and within 30min in pH6.8PBS. Pharmacolinetic experiment of Ondansetron Hydrochloric solution, marketed films Zuplenz® and the preparation were carried out in rats. As a result, the films of Ondansetron Hydrochloric containing ondansetron solid dispersion had the advantages of fast drug release, improved patient compliance, higher bioavalibility compared to oral solution and the marketed films.
昂丹司琼作为一种止吐药物已被广泛应用于治疗或预防呕吐性癌症化疗引起的恶心呕吐。快释膜具有快速释放药物和提高患者依从性的优点,尤其适用于卧床不起的残疾人、老年人或儿童患者。通过单因素试验对基本成膜材料进行了研究,并用固体分散技术对晶体抑制剂进行了优化。通过x射线衍射(XRD)和差示扫描量热法(DSC)对药物和聚合物的配比进行了优化,结果表明,优化后的固体分散体中不存在晶体。最终膜为白色薄膜,表面光滑,无明显气泡和裂纹。每片膜平均重量为40~50mg。平均厚度为60~70μm。表面pH值为6.4~6.6。在0.1mol/L HCl条件下,膜在1.5min内释放85%的药物,在pH6.8PBS条件下,膜在30min内释放85%的药物。对盐酸昂丹司琼溶液、市售薄膜Zuplenz®及其制剂进行了大鼠药动学实验。结果表明,与口服溶液和市售膜相比,含昂丹司琼固体分散体的盐酸昂丹司琼膜具有药物释放快、患者依从性好、生物利用度高等优点。
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引用次数: 0
Food preparation methods contribution to skin aging: a systematic review 食品制备方法对皮肤衰老的影响:系统综述
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/159417
M. Filipovic, D. Pecarski, J. Djordjević, M. Ivanović, V. Ilic, M. Lukić
Aging of the skin is a complex and multifactorial biological process, affected by different intrinsic and extrinsic factors. Exogenous factors affecting the process of skin aging, together with nutrition, are topics which currently draw considerable attention. Although it is difficult to accurately define what presents a healthy diet for maintenance of youthful skin, considering the evident lack of clinical data and studies in humans, there are numerous evidence suggesting that the food we eat affects our skin aging and its’ appearance. Well-documented is a fact that the modern diet is a large source of advanced glycation end products and reactive oxygen species – compounds formed during certain food preparation methods which accumulation is associated with different disease and recently, skin aging as well. This review gives the current state of knowledge related to the role which advanced glycation end products and reactive oxygen species, formed during the certain food preparation methods, have in the mechanisms of the premature/extrinsic skin aging. Additionally, it summarizes available information, in the form of recommendations for both the public and nutritional professionals who have an interest in this field, regarding food preparation methods and practices which prevent formation of aforementioned compounds in food and consequently could reduce the food contribution to premature skin aging.
皮肤老化是一个复杂的、多因素的生物过程,受到各种内在和外在因素的影响。影响皮肤老化过程的外源性因素与营养因素是目前备受关注的话题。考虑到缺乏临床数据和人体研究,虽然很难准确定义什么是维持年轻皮肤的健康饮食,但有大量证据表明,我们吃的食物会影响我们的皮肤老化及其外观。有充分证据表明,现代饮食是晚期糖基化终产物和活性氧的主要来源——在某些食物制备方法中形成的化合物,其积累与不同的疾病有关,最近也与皮肤老化有关。本文综述了在某些食品制备方法中形成的晚期糖基化终产物和活性氧在皮肤过早/外源性衰老机制中的作用。此外,它总结了现有的信息,以建议的形式提供给公众和对这一领域感兴趣的营养专业人士,关于食物制备方法和做法,防止上述化合物在食物中形成,从而减少食物对皮肤过早衰老的贡献。
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引用次数: 2
Temozolomide: a cytostatic drug that is still important today 替莫唑胺:一种至今仍很重要的细胞抑制药物
IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-03-03 DOI: 10.32383/appdr/159449
Kamil Dyrka, A. Czarnywojtek, M. Borowska, Jeremi Kościński, J. Moskal, N. Sawicka-Gutaj, A. Lewandowska, S. V. Van Gool, M. Fichna, P. Gut, K. Pietrończyk, Patryk Graczyk, M. Dworacka
TMZ has an advantage over other traditional alkylating agents (carmustine, lomustine, procarbazine), which are highly toxic and have poor patient survival. TMZ circumvents these problems because cytochrome P450 enzymes and the kidneys are not involved in its metabolism, it has predictable side effects (nausea, vomiting, thrombocytopenia, neutropenia), which are usually reversible and only mild to moderate, have been widely described.About half of patients treated with TMZ have high drug resistance induced by activity of O6-methylguanine methyltransferase. Cancer stem cells (CSCs), which are found among the neoplastic cell population, have also been shown to be responsible for resistance to TMZ. Additionally, acquired immunity, induced by TMZ’s epigenetic and genetic alterations, may develop. Currently, there are new therapeutic strategies for GBM based on nanotechnology, which are aimed at improving TMZ treatment (e.g. the use of apolipoprotein), or other techniques (siRNA, which increases the oxygen level in the tumour).Thus, although TMZ was discovered more than three decades ago, this drug will be used to treat not only GBM, but also a large number of neoplastic pathologies. Further research focused on understanding the mechanisms of action and resistance to TMZ is required to improve its clinical application today and in the future.Keywords: alkylating agents, drug resistance, chemotherapy, nanoparticles, cancer, glioblastoma multiforme
TMZ比其他传统的烷化剂(卡莫司汀、洛莫司汀和普鲁卡嗪)具有优势,后者毒性高,患者存活率低。TMZ避开了这些问题,因为细胞色素P450酶和肾脏不参与其代谢,它具有可预测的副作用(恶心、呕吐、血小板减少症、中性粒细胞减少症),这些副作用通常是可逆的,仅为轻度至中度,已被广泛描述。大约一半接受TMZ治疗的患者具有由O6甲基鸟嘌呤甲基转移酶活性诱导的高耐药性。在肿瘤细胞群中发现的癌症干细胞(CSCs)也被证明对TMZ具有耐药性。此外,TMZ的表观遗传学和遗传改变可能诱导获得性免疫。目前,基于纳米技术的GBM有新的治疗策略,旨在改善TMZ的治疗(例如使用载脂蛋白)或其他技术(siRNA,提高肿瘤中的氧气水平)。因此,尽管TMZ是在30多年前发现的,但这种药物不仅将用于治疗GBM,还将用于治疗大量肿瘤病理。需要进一步研究TMZ的作用机制和耐药性,以提高其在当今和未来的临床应用。关键词:烷化剂,耐药性,化疗,纳米颗粒,癌症,多形性胶质母细胞瘤
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引用次数: 0
期刊
Acta poloniae pharmaceutica
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