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PIM KINASES INHIBITORS AND PYRIMIDINE-BASED ANTICANCER AGENTS Pim激酶抑制剂和基于嘧啶的抗癌药物
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311247
Ibrahim Issa, A. Hammam, Helmy M. Sakr, RezkRezk A. Ayyad
Human phosphatidyl inositol mannoside kinases (Pim kinases) are important biological target for discovery of new anticancer agents. In addition, Pyrimidines have a good contribution as building blocks of many anticancer agents. Hence, a literature survey about Pim kinases inhibitors and pyrimidine-based anticancer agents have been achieved. In this survey, we introduced Pim kinase inhibitors under clinical assessment including imidazo[1,2-b ]pyridazines, isatins, thiazolidine-2,4-diones, pyridinamines, and diaminopyrazoles. In addition, Pim kinase inhibitors under development were presented. These compounds include pyridine-quinolines, benzimidazoles indoles, cyano pyridines, pyridothieno[3,2-d ]pyrimidin-4-ones, oxadiazole, and 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2 H )-ones. Furthermore, different pyrimidine-based anticancer agents have been discussed.
人磷脂酰肌醇甘露糖激酶(Pim激酶)是发现新的抗癌药物的重要生物学靶点。此外,嘧啶类化合物是许多抗癌药物的重要组成部分。因此,对Pim激酶抑制剂和基于嘧啶的抗癌药物进行了文献综述。在这项调查中,我们介绍了临床评估的Pim激酶抑制剂,包括咪唑[1,2-b]吡嗪类、异硫汀类、噻唑烷-2,4-二酮类、吡啶胺类和二氨基吡唑类。此外,还介绍了正在开发的Pim激酶抑制剂。这些化合物包括吡啶-喹啉、苯并咪唑-吲哚、氰基吡啶、吡啶噻吩[3,2-d]吡啶-4-酮、恶二唑和3,4-二氢吡咯[1,2-a]吡嗪-1(2h)-酮。此外,还讨论了不同的嘧啶类抗癌药物。
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引用次数: 0
COMPARATIVE STUDY AMONG FOUR SPECTROPHOTOMETRIC METHODS FOR THE SIMULTANEOUS DETERMINATION OF BINARY MIXTURE OF CHLORZOXAZONE AND DICLOFENAC POTASSIUM 四种分光光度法同时测定氯唑恶酮双氯芬酸钾二元混合物的比较研究
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311253
Rady F. Abdul-Kareem
Four simple, fast, accurate, reproducible, and non-sophisticated spectrophotometric methods were developed and validated for the simultaneous determination of chlorzoxazone and diclofenac potassium without preliminary separation in pure powder form and in their capsule formulation. Method A, is a dual wavelength spectrophotometric method in which the wavelengths selected for determination of chlorzoxazone were 259 nm and 294 nm, whereas the wavelengths selected for determination of diclofenac potassium were 294 nm and 242 nm. while method B, is a ratio difference spectrophotometric method in which the wavelengths selected for determination of chlorzoxazone were 280 nm and 230 nm, whereas the wavelengths selected for determination of diclofenac potassium were 246 nm and 284 nm. while method C, is the first derivative of the ratio spectra measured at 290 nm and 301 nm for chlorzoxazone and diclofenac potassium, respectively. While method D, is the constant center spectrophotometric method in which more measured at 280 nm and 277 nm for chlorzoxazone and diclofenac potassium, respectively. Regression analysis of Beer-Lambert’s plots showed good correlation in concentration range of 2.5 – 20 μg/mL for both drugs with LOD 0.308 μg/mL and 0.932 μg/mL, LOQ 0.458 μg/mL and 1.388 μg/mL, RSD 1.325 and 1.666 and % recovery 98.99 and 101.23 for chlorzoxazone and diclofenac potassium, respectively in method A. Furthermore, LOD 0.307 μg/mL and 0.373 μg/mL, LOQ 0.929 μg/mL and 1.123 μg/mL, RSD 1.065 and 1.371 and % recovery 99.94 and 101.53 for chlorzoxazone and diclofenac potassium, respectively in method B. Furthermore, LOD 0.287 μg/mL and 0.301 μg/mL, LOQ 0.871 μg/mL and 0.911 μg/mL, RSD 1.214 and 1.596 and % recovery 99.73 and 100.26 for chlorzoxazone and diclofenac potassium, respectively in method C. Furthermore, LOD 0.221 μg/mL and 0.331 μg/mL, LOQ 0.521 μg/mL and 0.825 μg/mL, RSD 0.914 and 1.412 and % recovery 101.22 and 98.59 for chlorzoxazone and diclofenac potassium, respectively in method D. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of chlorzoxazone and diclofenac potassium in their laboratory prepared mixtures and commercial capsule formulation.
建立了四种简单、快速、准确、重复性好、简便易行的分光光度法,可同时测定氯唑唑酮和双氯芬酸钾的含量,无需预先分离。方法A采用双波长分光光度法,测定氯唑唑酮的波长分别为259 nm和294 nm,测定双氯芬酸钾的波长分别为294 nm和242 nm。方法B为比值差分光光度法,测定氯唑唑酮的波长分别为280 nm和230 nm,测定双氯芬酸钾的波长分别为246 nm和284 nm。方法C为氯唑唑酮和双氯芬酸钾分别在290 nm和301 nm测得的比值光谱的一阶导数。方法D为恒中心分光光度法,分别在280 nm和277 nm处测定氯唑唑酮和双氯芬酸钾。beerlambert图回归分析表明,两种药物的浓度在2.5 ~ 20 μg/mL范围内相关性良好,方法a中氯唑唑酮和双氯芬酸钾的LOD分别为0.308 μg/mL和0.932 μg/mL, LOQ分别为0.458 μg/mL和1.388 μg/mL, RSD分别为1.325和1.666,回收率分别为98.99和101.23。方法a中氯唑唑酮和双氯芬酸钾的LOD分别为0.307 μg/mL和0.373 μg/mL, LOQ分别为0.929 μg/mL和1.123 μg/mL, RSD分别为1.065和1.371,回收率分别为99.94和101.53;氯唑唑酮和双氯芬酸钾的检出限分别为0.287和0.301 μg/mL,检出限分别为0.871和0.911 μg/mL, RSD分别为1.214和1.596,回收率分别为99.73和100.26。氯唑唑酮和双氯芬酸钾的检出限分别为0.221和0.331 μg/mL,检出限分别为0.521和0.825 μg/mL, RSD分别为0.914和1.412,回收率分别为101.22和98.59;方法d根据ICH指南进行了验证,并成功地应用于氯唑唑酮和双氯芬酸钾在实验室制剂和商业胶囊制剂中的含量测定。
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引用次数: 0
FORMULATION AND CHARACTERIZATIONS OF ROSUVASTATIN LOADED NANOSUSPENSION 瑞舒伐他汀纳米混悬液的制备与表征
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311236
Abdelhamid Elshafey, Sherif K. Abu-elyazid, A. Samy
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引用次数: 0
COMPARATIVE EVALUATION OF ANTICANCER AND ANTIBACTERIAL ACTIVITIES OF ENDOPHYTIC FUNGUS-DERIVED ZNO NANOPARTICLES AND CHEMICALLY SYNTHESIZED ZNO NANOPARTICLES 内生真菌衍生氧化锌纳米粒子与化学合成氧化锌纳米粒子抗癌和抗菌活性的比较研究
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311258
Hussein H. Elshikh, Sameh E. Hammad, M. El-rouby, M. Mostafa
Depending to the WHO, antibiotic resistance and limited anticancer and antimicrobial therapies continue to be serious worldwide health challenges. Current medicines' efficacy suffers by issues such as insufficient solubility, stability, and side effects. To create effective and dependable therapies against antibiotic resistance and robust illnesses, new techniques and strategies are required. Several metal nanoparticles synthesised via green synthesis or chemical synthesise, such as gold (Au), zine (ZnO), and others, have shown promising biological effects against malignancies and a wide spectrum of microbial illnesses caused by multi-drug resistant bacteria. An eco-friendly biosynthetic technique was used to create zinc oxide nanoparticles (ZnO NPs), as well as their antibacterial and anticarcinogenic activities. Extracellular synthesis of nanoparticles made of zinc oxide ZnO nanoparticles was achieved in the current work using the cell filtrate of the endophytic fungus Fusarium chlamydosporum MW341592.1 isolated from healthy leaves of Eucalyptus sideroxylon plant. The nanoparticles were characterised by UV-VIS spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transition electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The UV-Vis absorption spectra of the produced ZnO NPs showed bands in the UV area at (305) nm. Transmission electron microscopy TEM revealed average sizes of 19.3 nm, while shape revealed spherical like shape. The distinctive pattern of crystalline ZnO NPs was revealed by XRD diffract grams. Furthermore, Biological assay has shown that raising the nanoparticle concentration lowers the number of HCT-116 human colon cancer cells and CACO2 human intestinal cancer cells, as well as antibacterial pathogens Escherichia coli and Pseudomonas aeruginosa.
根据世界卫生组织的说法,抗生素耐药性和有限的抗癌和抗菌治疗仍然是世界范围内严重的健康挑战。目前药物的功效受到诸如溶解度、稳定性和副作用不足等问题的影响。为了创造有效和可靠的治疗抗生素耐药性和严重疾病的方法,需要新的技术和策略。通过绿色合成或化学合成的几种金属纳米颗粒,如金(Au)、锌(ZnO)等,已经显示出有希望的生物效应,可以治疗恶性肿瘤和多种由多重耐药细菌引起的微生物疾病。采用生态友好型生物合成技术制备氧化锌纳米颗粒(ZnO NPs),并研究其抗菌和抗癌活性。本研究利用桉木健康叶片内生真菌衣孢镰刀菌MW341592.1的细胞滤液,实现了氧化锌纳米颗粒的细胞外合成。采用紫外可见光谱(UV-VIS)、x射线衍射(XRD)、动态光散射(DLS)、透射电子显微镜(TEM)和能量色散x射线能谱(EDX)对纳米颗粒进行了表征。制备的ZnO纳米粒子紫外可见吸收光谱在(305)nm处出现紫外波段。透射电镜透射电镜显示平均尺寸为19.3 nm,形状呈球形。XRD衍射图揭示了ZnO纳米粒子的独特形态。此外,生物实验表明,提高纳米颗粒浓度可降低HCT-116人结肠癌细胞和CACO2人肠癌细胞的数量,以及抗菌病原体大肠杆菌和铜绿假单胞菌的数量。
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引用次数: 0
CHEMOMETRIC ASSISTED SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS DETERMINATION OF AMLODIPINE /CANDESARTAN MIXTURE IN THEIR PURE FORMS AND THEIR PHARMACEUTICAL PREPARATIONS 化学计量辅助分光光度法同时测定纯氨氯地平/坎地沙坦混合物及其制剂的含量
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311252
Ahmed W. Madkour
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引用次数: 0
GREEN CHEMOMETRIC ASSISTED SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF CIPROFLOXACIN, METRONIDAZOLE, AND INDOMETHACIN RESIDUES IN PHARMACEUTICAL INDUSTERIAL WASTEWATER EFFLUENTS 绿色化学计量辅助分光光度法测定制药工业废水中环丙沙星、甲硝唑和吲哚美辛残留量
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311248
Islam Selim, Osama I Abdel Sattar, Hamed H M Abuseada, Mohamed S. Emara, A. Serag
Development and validation of three simple, eco-friendly, accurate and precise chemometric models have been presented for the spectrophotometric determination of ciprofloxacin (CIP), indomethacin (IND), and metronidazole (MET) residues in production wastewater samples. These methods are classical least square (CLS), principal component regression (PCR) and partial least square (PLS-1). A 3-factor 5-level experimental design was built leading to 25 mixtures containing different ratios of CIP, MET, and IND. Thirteen mixtures were used as a training set, and the other twelve were used as a validation set. Using of multi-wavelengths instead of the single wavelength spectrophotometry has greatly improved the precision and predictive abilities of these multivariate calibrations. The proposed methods have been found to be accurate, precise and can be used for determination of the drugs in pure form and industrial wastewater samples without preliminary separation steps. The methods described were used to accurately assess the drug residues in laboratory-prepared mixtures and actual industrial wastewater samples to confirm that it is free from these drug residues so it can be recycled and used for irrigation and other purposes.
建立了三种简单、环保、准确、精密的化学计量模型,用于生产废水中环丙沙星(CIP)、吲哚美辛(IND)和甲硝唑(MET)残留的分光光度测定。这些方法是经典最小二乘法(CLS)、主成分回归(PCR)和偏最小二乘法(PLS-1)。建立了一个3因素5水平的实验设计,包括25个含有不同比例CIP、MET和IND的混合物。其中13个混合物作为训练集,另外12个作为验证集。采用多波长分光光度法代替单波长分光光度法,大大提高了这些多元校准的精度和预测能力。结果表明,该方法准确、精确,可用于纯形式和工业废水样品的测定,无需预先分离步骤。所描述的方法用于准确评估实验室制备的混合物和实际工业废水样品中的药物残留,以确认其不含这些药物残留,从而可以回收并用于灌溉和其他目的。
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引用次数: 0
REVIEW ON THE SIGNIFICANCE OF PYRIMIDINE DERIVATIVES AS POTENT ANTI-ANGIOGENIC VEGFR-2 INHIBITORS 嘧啶衍生物作为抗血管生成vegf -2抑制剂的意义综述
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311245
Ibrahim Issa, Abdulrahman M. Saleh, M. Khalifa, H. Mahdy
Cancer is a disease in which human cells grow uncontrollably and spread to other body parts. Cancer is the second leading cause of death globally and accounted for 9.6 million deaths in 2022 according to the statistics of the World Health Organization. Cancer can begin in any part of the human organs when the normal cell loses the ability to control the division cycle, which may inhibit apoptosis. Cancer cells grow and multiply by activating the angiogenetic factors to build new capillaries that can supply tumor tissue with nutrients. Cancerous tumors spread into or invade nearby tissues and can travel to other organs in the body to form new carcinogenic tissue by metastasis. The goal of treatment is control growth of cancer cells, and induction the programmed cell death. Pyrimidines and its derivatives have been found as effective and valuable pharmacophoric units in medicinal chemistry to design and develop a wide range of bioactive compounds. The present review summarizes the advances in lead compounds of pyrimidines hybrids and their related heterocycles in the treatment of cancer. Moreover, the review also helps to intensify the drug development process by providing an understanding of the potential role of these hybridized pharmacophoric features as VEGFR-2 inhibitors.
癌症是一种人体细胞不受控制地生长并扩散到身体其他部位的疾病。癌症是全球第二大死因,根据世界卫生组织的统计,2022年癌症造成960万人死亡。当正常细胞失去控制分裂周期的能力时,癌症可以在人体器官的任何部位开始,这可能会抑制细胞凋亡。癌细胞通过激活血管生成因子来生长和繁殖,从而建立新的毛细血管,为肿瘤组织提供营养。癌性肿瘤扩散或侵入附近组织,并可通过转移转移到身体其他器官形成新的致癌组织。治疗的目的是控制癌细胞的生长,诱导细胞程序性死亡。嘧啶及其衍生物在药物化学中是一种有效的、有价值的药效单位,可用于设计和开发各种具有生物活性的化合物。本文综述了嘧啶类杂环先导化合物及其相关杂环化合物在癌症治疗中的研究进展。此外,通过了解这些杂交的药理特征作为VEGFR-2抑制剂的潜在作用,该综述还有助于加强药物开发过程。
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引用次数: 0
THE PREVALENCE OF DERMATOPHYTOSIS, ITS RELATIONSHIP TO BLOOD TYPE AND DISEASE MANAGEMENT HOSPITAL BASED STUDY IN EGYPT 埃及皮肤癣患病率、血型关系及疾病管理的医院研究
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311255
Y. Elsaba, M. Osman, Ayman Ahmed, Mahmoud E. Esmael, Hagar Abdelkareem
The aim of this study was to investigate the common dermatophytosis and dermatophyte(s) in Cairo hospitals, examining age, gender, blood groups, and dermatophyte incidence. It explores natural extracts like plant oils and fungal extracts as alternatives to commercial antifungal drugs and their synergistic effects. In this study, the prevalence of distinct types of dermatophytosis was investigated in 128 patients who were referred to the dermatology departments of different hospitals, including EL-Houd El-Marsoud, El Zahraa Medical Hospital, and El-Sahel Teaching Hospital in Cairo, Egypt. Descriptive data for the tested patients was collected, including age, gender, the source of infection, and blood group type. The results showed that Tinea capitis was the most prevalent dermatophytosis, mostly in children. Investigating the correlation between blood group types and the incidence of the disease revealed that patients with blood groups B and O were the most sensitive ones. The most prevalent dermatophyte within the studied cases was identified and submitted to GenBank as Microsporum canis ON564613. To investigate the effectiveness of antifungal agents against M. canis , different common antifungal drugs, including terbinafine, ketoconazole, clotrimazole, fluconazole, and betadine
本研究的目的是调查开罗医院常见的皮肤癣病和皮肤癣菌,检查年龄、性别、血型和皮肤癣菌发病率。它探索天然提取物,如植物油和真菌提取物作为商业抗真菌药物的替代品及其协同作用。在这项研究中,研究人员调查了在埃及开罗的El- houd El- marsoud、El- Zahraa医院和El- sahel教学医院等不同医院皮肤科转诊的128名患者不同类型皮肤癣的患病率。收集检测患者的描述性数据,包括年龄、性别、感染源和血型。结果表明,头癣是最常见的皮肤病,以儿童为主。调查血型与疾病发病率的相关性发现,B型血和O型血的患者最为敏感。研究病例中最常见的皮肤真菌被鉴定并提交给GenBank,编号为Microsporum canis ON564613。探讨常用抗真菌药物特比萘芬、酮康唑、克霉唑、氟康唑和倍他定对犬支原体的抗真菌效果
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引用次数: 0
RECENT ADVANCES ON PYRIMIDINE DERIVATIVES AS ANTICANCER AGENTS. 嘧啶衍生物抗癌研究进展。
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311246
H. Mahdy, Hany Elnagar, Helmy M. Sakr
Cancer is a global health challenge; it impacts the quality of life and its treatment is associated with several side effects. Resistance of the cancer cells to the existing drugs has led to search for novel anticancer agents. Pyrimidine, a privileged scaffold, is part of living organisms and plays vital role in various biological procedures as well as in cancer pathogenesis. Due to resemblance in structure with the nucleotide base pair of DNA and RNA, it is recognized as valuable compound in the treatment of cancer.
癌症是一项全球健康挑战;它会影响生活质量,其治疗与几种副作用有关。癌细胞对现有药物的耐药性促使人们寻找新的抗癌药物。嘧啶作为一种特殊的支架,是生物体的一部分,在各种生物过程和癌症发病中起着至关重要的作用。由于与DNA和RNA的核苷酸碱基对结构相似,被认为是治疗癌症的有价值的化合物。
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引用次数: 0
PREPARATION AND EVALUATION OF SUSTAINED RELEASE MATRIX FORMULATIONS OF VORICONAZOLE 伏立康唑缓释基质制剂的制备与评价
Pub Date : 2023-03-01 DOI: 10.21608/ajps.2023.311244
Shereen Abd El Gawad, M. Marzouk, A. Ammar
Voriconazole is a triazole antifungal with a half-life of 1.7 hours and 96% oral bioavailability. The oral route is the most popular of drug delivery routes. However, there are a few limitations to the traditional dosage form, for instance, fluctuations in plasma drug level. Sustained drug delivery system overcomes these limitations; it helps to maintain stable plasma drug concentrations by decreasing drug r elease and extending the duration of the effect. The main purpose of this study was to formulate voriconazole sustained release dosage form to enhance efficacy, decrease dose frequency, decrease its side effects, and improve patient compliance. The study explored various formulations for producing the sustained-release (S.R) dosage form, as well as assessed the drug's release kinetics and its stability. Methodology : Fourier-transform Infrared Spectroscopy was used to investigate drug-polymer compatibility. The micromeritics of voriconazole powder and its blends were evaluated. Different sustained release tablets were formulated utilizing a wet granulation process and acrylic polymers (Eudragit) i.e., Eudragit RL100 and RS100 alone and as mixtures with different ratios, in different concentrations. In-vitro drug release of formulae was performed for 24 hours. The formula with desired control of drug release and complied with dissolution specifications for SR dosage forms was further evaluated for its stability by storage for 3 months at 30 o C and 40 o C and 75% relative humidity. Results : no interaction was observed between voriconazole and polymers using FTIR. The powder blends micromeritics were found to be in accordance with the specification. Tablets showed release from 37.29 to 76 % up to 24 hr using USP type I technique. It was found that as polymer concentration increased, the drug release from tablet decreased. The selected formulation F13 which containing 5% of Eudragit RL100:RS100 at a ratio of (10:1) was found to be stable. Conclusion : The obtained data concluded that the F13 formula gave more prominent S.R effect than using Eudragit RL100 or RS 100 alone.
伏立康唑是一种三唑类抗真菌药物,半衰期为1.7小时,口服生物利用度为96%。口服给药途径是最常用的给药途径。然而,传统的剂型存在一些局限性,例如,血浆药物水平的波动。持续给药系统克服了这些限制;它通过减少药物释放和延长作用时间来帮助维持稳定的血浆药物浓度。本研究的主要目的是制定伏立康唑缓释剂型,以提高疗效,减少给药频率,减少副作用,提高患者依从性。本研究探索了生产缓释剂型的各种配方,并评估了药物的释放动力学和稳定性。方法:采用傅里叶变换红外光谱法研究药物-聚合物的相容性。对伏立康唑粉末及其共混物进行了显微测量。不同的缓释片采用湿造粒工艺和丙烯酸聚合物(Eudragit),即Eudragit RL100和RS100单独以及不同比例,不同浓度的混合物配制。体外释放时间为24小时。通过在30℃、40℃、75%相对湿度条件下贮存3个月,进一步评价该制剂的稳定性。结果:伏立康唑与聚合物在FTIR中未见相互作用。粉末共混物的显微指标符合规定。使用USP I型技术,片剂在24小时内释放率为37.29% ~ 76%。结果表明,随着聚合物浓度的增加,药物释放量减小。所选择的配方F13,含5%乌龙茶RL100:RS100,比例为(10:1),稳定性较好。结论:所得数据表明,F13配方比乌龙茶RL100或单独使用乌龙茶RL100具有更显著的S.R效果。
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引用次数: 0
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Al-Azhar Journal of Pharmaceutical Sciences
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