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Screening of new morpholine dithiocarbamate derivatives bearing benzimidazole moiety for anticholinesterase potential 含有苯并咪唑基团的新型二硫代氨基甲酸啉衍生物抗胆碱酯酶潜力的筛选
Pub Date : 2023-08-28 DOI: 10.55971/ejls.1328405
H. Temel, Gülşen Akalın Çiftçi, L. Yurttaş
Alzheimer’s disease (AD) is basically associated with disturbances of cholinesterase metabolism which result in acetylcholine deficiency. Target of acetylcholinesterase (AChE) inhibitors used in symptomatic therapy of disease is to increase of ACh levels. Consequently, cholinesterase inhibitors were developed to increase acetylcholine is to inhibit AChE and butrylcholinesterase (BuChE). Studies demonstrate the clinical importance of dual inhibitors that inhibit not only the acetylcholinesterase enzyme but also the butyrylcholinesterase enzyme.In recent years, benzimidazoles have attracted particular interest owing to their anticolinesterase activity. In this manner, we have synthesized benzimidazole and morpholine including compounds (2a-i). Final compounds were achieved with the reaction of (benzimidazol-2-yl) methyl morpholine-4-carbodithioate and α-bromoacetophenone derivatives in acetone at room temperature with stirring. Inhibition effects of novel morpholine dithiocarbamates (2a-i) were tested on AChE and BuChE. Compound 2d demonstrated dual inhibitory activity on AChE and BuChE (78±1,56, 70,71±1,53, respectively), with the lowest cytotoxicity to normal cell line.
阿尔茨海默病(AD)基本上与胆碱酯酶代谢紊乱导致乙酰胆碱缺乏有关。乙酰胆碱酯酶(AChE)抑制剂用于疾病对症治疗的目标是提高乙酰胆碱酯酶水平。因此,开发了胆碱酯酶抑制剂,以增加乙酰胆碱,抑制乙酰胆碱酯酶和丁胆碱酯酶(BuChE)。研究表明,既抑制乙酰胆碱酯酶又抑制丁基胆碱酯酶的双重抑制剂具有重要的临床意义。近年来,苯并咪唑因其抗大肠杆菌酯酶活性而引起了人们的特别关注。用这种方法,我们合成了含化合物(2a-i)的苯并咪唑和啉。以(苯并咪唑-2-酰基)甲基吗啡啉-4-碳二硫酸酯与α-溴苯乙酮衍生物在丙酮中室温搅拌反应得到最终化合物。研究了新型二硫代氨基甲酸啉(2a-i)对AChE和BuChE的抑制作用。化合物2d对AChE和BuChE具有双重抑制活性(分别为78±1、56、70、71±1、53),对正常细胞系的细胞毒性最低。
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引用次数: 0
The role of immunotherapy in lung cancer: Actual scenery 免疫治疗在肺癌中的作用:实景
Pub Date : 2023-04-24 DOI: 10.55971/ejls.1267898
Ipek Ertorun, Aydan Huseynli, Sevinc Nursena Ertekın, Gülşen Akalın Çiftçi
More than half of those who succumb to cancer each year also lose their battle with the disease, making cancer a leading cause of death worldwide. After surgery, hormonal therapy, radiotherapy and chemotherapy, which are preferred in cancer management, immunotherapy has revolutionized. In this mini-review, we cover the various immunotherapeutic approaches used in contemporary cancer immunotherapies. These are immune checkpoint blockade, an attemp planned to ‘unleash’ robust T cell responses, and adaptive cellular therapies connected on the infusion of tumor-struggling immune cells into the body. One of these attemps, Nivolumab, became the first ICI to be approved to treat lung cancer in 2014. To date, different ICIs, such as pembrolizumab, atezolizumab, and durvalumab, have been in a row introduced into clinical medicine and have shown significant effect. Therefore, in this mini-review, we present some emerging goals and attemps in cancer immunotherapy.
每年死于癌症的人中,有一半以上的人也失去了与疾病的斗争,使癌症成为世界范围内死亡的主要原因。在手术,激素治疗,放疗和化疗,这些在癌症治疗中首选之后,免疫治疗已经发生了革命性的变化。在这篇简短的综述中,我们涵盖了当代癌症免疫治疗中使用的各种免疫治疗方法。它们是免疫检查点封锁,一种计划“释放”强大的T细胞反应的尝试,以及与肿瘤免疫细胞注入体内相关的适应性细胞疗法。2014年,Nivolumab成为首个被批准用于治疗肺癌的ICI。迄今为止,不同的ICIs如pembrolizumab, atezolizumab和durvalumab已连续引入临床医学并显示出显着的效果。因此,在这篇综述中,我们提出了癌症免疫治疗的一些新目标和尝试。
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引用次数: 0
Determination of potential probiotic properties of lactic acid bacteria isolated from colostrum milk 初乳分离乳酸菌潜在益生菌特性的测定
Pub Date : 2023-04-24 DOI: 10.55971/ejls.1263343
P. Soyer, Melek Tekgöz, Y. Tunalı
Colostrum milk has been used as a source for isolating many probiotic bacteria since it contains many helpful probiotic microorganisms. Because of the huge microorganism diversity and functionality of colostrum, there is opportunity to isolate bacteria and analyze their probiotic potential. Comparing the diversity of probiotic bacteria in milk from postpartum periods is also crucial. In the current study, Lactic Acid Bacteria (LAB) cultures were isolated from cow colostrum milk. The 28 cultures were isolated, but only 2 were characterized as LAB by their colony and molecular characterization, Gram nature, catalase, antibiotics, and pepsin tolerance. As a result of molecular identification tests, the isolates were identified as Lactobacillus casei and Lactobacillus paracasei with 99-100% homology. These two isolates could survive in the presence of gastric and intestinal conditions. These isolates also showed antimicrobial and antioxidant activities. The results demonstrated that LAB species isolated from colostrum milk exhibited promising probiotic properties and seemed favorable for use in pharmaceuticals and foods.
初乳已被用作分离许多益生菌的来源,因为它含有许多有益的益生菌微生物。由于初乳具有丰富的微生物多样性和功能性,因此有机会分离细菌并分析其益生菌潜力。比较产后牛奶中益生菌的多样性也很重要。本研究从牛初乳中分离乳酸菌(LAB)培养物。28个培养物被分离出来,但只有2个通过菌落和分子特征、革兰氏性质、过氧化氢酶、抗生素和胃蛋白酶耐受性被鉴定为LAB。分子鉴定结果表明,分离物为干酪乳杆菌和副干酪乳杆菌,同源性为99 ~ 100%。这两株菌株在胃和肠道条件下均能存活。这些分离物还具有抗菌和抗氧化活性。结果表明,从初乳中分离出的乳酸菌具有良好的益生菌特性,有望用于制药和食品领域。
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引用次数: 0
Knowledge and behavior of community pharmacists towards detecting drug-drug interactions 社区药剂师对检测药物-药物相互作用的知识和行为
Pub Date : 2023-04-24 DOI: 10.55971/ejls.1266042
F. Oğuz, M. Arslan
Drug-drug interactions (DDIs) are preventable medication errors that can cause severe adverse effects for patients, which often involve more than one mechanism. Healthcare practitioners, especially community pharmacists, must know and manage potentially significant DDIs to provide patient safety.This paper mainly aims to determine the knowledge level of community pharmacists about DDIs and to evaluate the behavior of community pharmacists in detecting DDIs. For this aim, a face-to-face questionnaire, including a knowledge assessment test containing 20 drug pairs and ten behavior statements related to detecting DDIs, was applied to community pharmacists.Seventy-three pharmacists participated in the study. The study’s findings show that the knowledge level of community pharmacists, who are the closest health consultants, about DDIs is relatively low. In addition, responses were found to be moderate in detecting drug interactions.Although statistically significant and positive effects of vocational training on the knowledge level and behaviors of pharmacists were determined, it was revealed that education levels did not have a significant effect.In this regard, it is essential to improve community pharmacists’ DDI knowledge level through vocational training programs and encourage their interaction-detecting behavior to improve patient outcomes and patient safety.
药物-药物相互作用(ddi)是可预防的药物错误,可对患者造成严重的不良反应,通常涉及不止一种机制。医疗保健从业人员,特别是社区药剂师,必须了解和管理潜在的重要ddi,以提供患者安全。本文主要旨在了解社区药师对ddi的了解程度,评价社区药师检测ddi的行为。为此,对社区药师进行面对面问卷调查,包括包含20种药物对和10种与检测ddi相关的行为陈述的知识评估测试。73名药剂师参与了这项研究。研究结果表明,社区药剂师是最接近健康顾问的人,他们对DDIs的知识水平相对较低。此外,在检测药物相互作用方面,反应被发现是温和的。虽然职业培训对药师的知识水平和行为有显著的正向影响,但教育水平对药师的知识水平和行为的影响并不显著。因此,必须通过职业培训项目提高社区药师的DDI知识水平,并鼓励其互动检测行为,以改善患者预后和患者安全。
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引用次数: 0
Synthesis, biological activity evaluation and molecular docking studies of novel thiazole derivatives 新型噻唑衍生物的合成、生物活性评价及分子对接研究
Pub Date : 2023-04-24 DOI: 10.55971/ejls.1270394
Derya Osmaniye, Uğur Kayış, Ü. Gül, Y. Özkay, Z. Kaplancıklı
Resistance to existing drugs develops because of insensible use of antibacterial and antifungal drugs. Therefore, there is a need for the development of new drug candidate compounds. The thiazole ring has many biological activities. It is possible to include antibacterial and antifungal activities among these activities. In addition to these, the thiazole ring has been preferred because it is the bioisostere of the imidazole ring in the structure of many antifungal drugs. For this purpose, within the scope of this study, 7 new thiazole compounds were synthesized, and their structure determinations were carried out using HRMS, 1H-NMR, 13C-NMR spectroscopic methods. Their antibacterial and antifungal activities were investigated by in vitro methods. As a result of activity tests, compound 3e showed activity against C.krusei strain with MIC50=31.25 ug/mL. The potential effectiveness of the compound 3e on the 14alpha-demethylase enzyme (PDB ID:3LD6) was tested by in silico studies.
由于不明智地使用抗菌和抗真菌药物,对现有药物产生耐药性。因此,有必要开发新的候选药物化合物。噻唑环具有许多生物活性。在这些活性中可能包括抗菌和抗真菌活性。除此之外,噻唑环一直是首选的,因为在许多抗真菌药物的结构中,它是咪唑环的生物同分异构体。为此,在本研究范围内,合成了7个新的噻唑类化合物,并利用HRMS、1H-NMR、13C-NMR等波谱方法对其结构进行了测定。采用体外抑菌法研究其抑菌活性。活性试验表明,化合物3e对克氏弧菌的抑菌活性最高,MIC50=31.25 ug/mL。化合物3e对14 α -去甲基化酶(PDB ID:3LD6)的潜在有效性通过硅实验进行了测试。
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引用次数: 1
An observational study on drug interactions caused by proton pump inhibitors 质子泵抑制剂引起药物相互作用的观察性研究
Pub Date : 2023-04-24 DOI: 10.55971/ejls.1209405
Betül Aykut, M. Arslan
Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related diseases worldwide and in our country. The high reliability of PPIs also allows long-term use for appropriate indications in chronic diseases, which increases the possibility of drug-drug interactions. Therefore, it is clear that the usage of PPIs should be monitored in terms of drug-drug interactions to provide drug treatment success and patient safety. The ability of pharmacists, the closest health consultants, to identify these interactions during prescription fulfillment will significantly contribute to treatment success. Although many studies deal with the rational use of PPIs and drug interactions, the number of studies revealing observational drug interactions is minimal. This research aims to determine drug-drug interactions frequently encountered in community pharmacies for PPIs, which interact with many drug groups and are commonly prescribed. For this purpose, approximately 1700 prescriptions supplied by a selected community pharmacy, serving in Van, were examined. One hundred sixty-four of the prescriptions were evaluated by considering the study’s limitations. Drug-drug interactions were checked by three different electronic database. It was determined that 73 of 164 prescriptions had interactions in at least one of the three databases. In 73 prescriptions, 86 drug interactions were observed. 34% of the interactions detected in the study were caused by lansoprazole.
质子泵抑制剂(PPIs)在国内外广泛用于治疗胃酸相关疾病。PPIs的高可靠性也允许长期用于慢性病的适当适应症,这增加了药物-药物相互作用的可能性。因此,很明显,PPIs的使用应在药物相互作用方面进行监测,以提供药物治疗的成功和患者的安全。药剂师,最亲密的健康顾问,在处方履行过程中识别这些相互作用的能力将显著有助于治疗成功。尽管许多研究涉及PPIs的合理使用和药物相互作用,但揭示观察性药物相互作用的研究数量很少。本研究旨在确定PPIs在社区药房经常遇到的药物-药物相互作用,PPIs与许多药物组相互作用,通常是处方药。为此目的,审查了凡市一个选定的社区药房提供的大约1700张处方。考虑到研究的局限性,对164种处方进行了评估。药物-药物相互作用通过三个不同的电子数据库进行检查。确定164个处方中有73个在三个数据库中的至少一个中有相互作用。在73张处方中,观察到86种药物相互作用。研究中检测到的34%的相互作用是由兰索拉唑引起的。
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引用次数: 0
Focusing on the moderately active compound (MAC) in the design and development of strategies to optimize the apoptotic effect by molecular mechanics techniques 重点研究适度活性化合物(MAC)的设计和开发策略,利用分子力学技术优化细胞凋亡效应
Pub Date : 2023-02-28 DOI: 10.55971/ejls.1209591
A. Evren, Demokrat Nuha, L. Yurttaş
Today, chemotherapeutic agents are mostly used to fight cancer in clinics. But even though they have selectivity for cancer cells, their mechanism of action could result in necrosis. Therefore, we aimed to suggest new design strategies using a moderately active compound (MAC) to get better activity and increase the apoptotic effect in this study. Although MAC, previously synthesized and evaluated for its anticancer properties, has been marked as a moderately active compound, it has let us develop new molecules using its molecular core supported by molecular docking and molecular dynamics simulation. The caspase-3 enzyme was subjected to density functional theory (DFT), docking, and molecular dynamics simulation studies, and the results were analyzed to better understand the structure-activity relationship (SAR); thus, new design strategies were proposed.
今天,化疗药物主要用于临床治疗癌症。但即使它们对癌细胞有选择性,它们的作用机制也可能导致坏死。因此,在本研究中,我们旨在提出新的设计策略,使用中等活性化合物(MAC)来获得更好的活性并增加凋亡作用。虽然之前已经合成并评估了其抗癌特性的MAC被标记为中等活性化合物,但我们可以利用它的分子核心在分子对接和分子动力学模拟的支持下开发新分子。对caspase-3酶进行密度泛函理论(DFT)、对接和分子动力学模拟研究,并对结果进行分析,以更好地了解其构效关系(SAR);因此,提出了新的设计策略。
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引用次数: 1
Latest research about active pharmaceutical ingredient loaded Poly Lactic Acid-co-Glycolic Acid (PLGA) based drug delivery system in Türkiye 活性药物成分负载聚乳酸-羟基乙酸(PLGA)为基础的体外给药系统研究进展
Pub Date : 2023-02-24 DOI: 10.55971/ejls.1197082
Berna Kaval, Fatma Şen, Kemal Kaya Batmaz, Meliha Ekinci, A. A. Öztürk
Some of the most well-engineered and produced biomaterials are polyesters based on polyglycolic acid (PGA), polylactic acid (PLA), and their copolymers, polylactic acid co-glycolic acid (PLGA). In controlled release systems, PLGA is the most extensively used and popular polymer. Because of its biodegradability, biocompatibility, and favorable release kinetics, but also because of the reliability of protein delivery issues, this synthetic polymer has been found to be very successful. PLGA is approved in various human drug delivery systems by EMA and FDA. In this review, first, PLGA and historical development, usage, physico-chemical structure, drug release properties, degredation specifications, solubility, crystallinity, thermal stability, release properties, types of PLGA will be mentioned. In the last stage of the review, studies conducted in Türkiye are included. In conclusion, we believe that this review is a resource for researchers doing research with PLGA.
一些最精心设计和生产的生物材料是基于聚乙醇酸(PGA),聚乳酸(PLA)及其共聚物聚乳酸共乙醇酸(PLGA)的聚酯。在控释系统中,PLGA是应用最广泛和最受欢迎的聚合物。由于其生物可降解性、生物相容性和良好的释放动力学,也由于蛋白质递送的可靠性问题,这种合成聚合物被发现是非常成功的。PLGA已被EMA和FDA批准用于各种人类药物输送系统。本文首先介绍了PLGA的历史发展、用途、理化结构、释药性能、降解规格、溶解度、结晶度、热稳定性、释药性能、PLGA的种类。在审查的最后阶段,包括在 rkiye进行的研究。总之,我们相信这篇综述对研究PLGA的研究人员来说是一个资源。
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引用次数: 0
Essential oil composition and antimicrobial activity of Glaucosciadium cordifolium (Boiss.) Burtt. & Davis 青花草精油成分及抑菌活性研究伯特。和戴维斯
Pub Date : 2023-02-24 DOI: 10.55971/ejls.1215741
N. Saltan, A. Kaya, G. İşcan, B. Demirci
Glaucosciadium cordifolium (Boiss.) Burtt. & Davis, which is a monotypic species naturally grown in Turkey belonging to the Apiaceae (Umbelliferae) family. In this study, the essential oil obtained from G. cordifolium was analyzed and evaluated for its antimicrobial effects. In chemical studies, the analyzes of essential oil compounds obtained from the aerial parts of plants by hydrodistillation were carried out with GC-FID and GC-MS. In total, 23 compounds were identified making up 98.7% of the total volatile constituents. Sabinene (42.1%), α-pinene (17.1%), and α-phellandrene (10.1%) were found as the main constituents in the oil.In antimicrobial studies, the anticandidal and antibacterial effects of essential oils were tested against 14 pathogenic microorganisms according to the standard protocols of the Clinical Laboratory Standards Institute (CLSI). It has been determined that essential oils have a very weak inhibitory effect when compared with standard antibacterial agents. MIC values of 1800, 3600 µg/Ml, and higher were determined. In addition, it was determined that it showed inhibitory effects, especially against C. krusei at a concentration of 250 µg/mL, with MIC values ranging from 250 to 2000 µg/mL.
青花草(植物科)伯特。这是一种在土耳其自然生长的单型物种,属于伞形科(伞形科)家族。在本研究中,分析和评价了从芫荽中提取的精油的抗菌作用。在化学研究方面,采用气相色谱- fid和气相色谱-质谱联用技术对植物气相蒸馏法提取的挥发油化合物进行了分析。共鉴定出23种化合物,占总挥发性成分的98.7%。主要成分为沙宾烯(42.1%)、α-蒎烯(17.1%)和α-费蓝烯(10.1%)。在抗菌研究中,根据临床实验室标准协会(CLSI)的标准方案,对精油对14种病原微生物的抗药和抗菌作用进行了测试。经测定,与标准抗菌剂相比,精油的抑菌作用非常弱。测定的MIC值为1800、3600µg/Ml及更高。此外,测定其具有抑制作用,特别是在浓度为250µg/mL时,其MIC值为250 ~ 2000µg/mL。
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引用次数: 0
Arum italicum Miller tuber extracts: evaluation of synergistic activities with ciprofloxacin against some pathogens 意大利魔芋提取物:与环丙沙星对某些病原体协同作用的评价
Pub Date : 2023-02-24 DOI: 10.55971/ejls.1148283
H. G. Ağalar, Gözde Öztürk, N. Kirimer
Antibiotic misuse or overuse leads antibiotic resistance. Antibiotic resistant bacteria infections cause significant clinical problem. Recently, antibiotic resistant bacteria numbers have increased, this situation has become a global public health treat. To achieve these problems, development of new antibacterial compounds is still popular among researchers. The focus on natural compounds/plant extracts in combination with antibiotics increase their activities and decrease the doses of antibiotics and their side effects. Despite known as poisonous, Arum italicum Miller is used as food and/or is used for the treatment such ailments as furuncle, eczema, peptic ulcer, wounds, etc. This interesting species was found as anticancer, cytotoxic, apoptotic agent against some human cancers. In the present study, the fractions of A. italicum tuber extract against human pathogens (Pseudomonas aeruginosa ATCC 27853, Bacillus cereus NRRL B-3711, Staphylococcus aureus ATCC 6538) were evaluated for their antibacterial activities by microdilution method. Each fraction was combined with ciprofloxacin and their synergistic activities were tested by checkerboard method. The MIC (minimum inhibitory concentrations) and FICI (fractional inhibitory concentration indexes) values were calculated. Totally, seven synergic interactions, ten additive interactions, and four indifferent interactions of tested fractions with ciprofloxacin were found.
抗生素滥用或过度使用导致抗生素耐药性。抗生素耐药菌感染引起严重的临床问题。近年来,抗生素耐药菌数量有所增加,这一情况已成为全球公共卫生的一大难题。为了解决这些问题,开发新的抗菌化合物仍然受到研究人员的欢迎。对天然化合物/植物提取物与抗生素结合的关注增加了它们的活性,减少了抗生素的剂量及其副作用。尽管被认为是有毒的,但意大利魔芋被用作食物和/或用于治疗诸如疖、湿疹、消化性溃疡、伤口等疾病。这个有趣的物种被发现对某些人类癌症具有抗癌、细胞毒性和细胞凋亡作用。本研究采用微量稀释法测定了意大利香根提取物对铜绿假单胞菌ATCC 27853、蜡样芽孢杆菌NRRL B-3711、金黄色葡萄球菌ATCC 6538等人体病原菌的抑菌活性。将各组分与环丙沙星配伍,采用棋盘法测定其增效活性。计算最小抑菌浓度MIC和分数抑菌浓度指数FICI值。共发现7种协同相互作用,10种加性相互作用,4种无差异相互作用。
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引用次数: 0
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European Journal of Life Sciences
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