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Molecular Targets of Plant-based Alkaloids and Polyphenolics in Liver and Breast Cancer- An Insight into Anticancer Drug Development. 肝癌和乳腺癌中植物生物碱和多酚类化合物的分子靶点--抗癌药物开发的启示。
IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-07-03 DOI: 10.2174/0118715206302216240628072554
Salma Batool, Laiba Asim, Fawad Raffaq Qureshi, Ammara Masood, Maria Mushtaq, Rahman Shah Zaib Saleem

Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.

肝癌和乳腺癌是最常见的癌症,导致癌症相关死亡率居高不下。癌症是一种威胁生命的疾病,影响着全球人口,因此有必要开发新型疗法。现有的治疗方法包括放疗、化疗、手术和免疫疗法。最先进的现代方法是使用植物提取的抗癌药物,这些药物能够靶向癌细胞并抑制其增殖。一般认为,植物提取的化合物比合成药物/传统疗法更安全,可作为治疗肝癌和乳腺癌的潜在新靶点,从而彻底改变癌症治疗方法。生物碱和多酚已被证明可通过分子方法发挥抗癌作用。它们能破坏各种细胞机制,抑制细胞周期蛋白和 CDK 的产生,使细胞周期停止,并通过上调 p53、p21 和 p38 的表达激活 DNA 修复机制。在无法修复的严重情况下,它们会通过激活 Caspase-3、8 和 9 以及增加 Bax/Bcl-2 比率来诱导肝癌和乳腺癌细胞凋亡。它们还能使多种信号通路失活,如 PI3K/AKT/mTOR、STAT3、NF-kB、Shh、MAPK/ERK 和 Wnt/β-catenin 通路,从而控制癌细胞的发展和转移。本综述的亮点在于对癌症中至关重要的特定蛋白质表达的调控,例如在 HER2 过度表达的乳腺癌细胞中;有报道称生物碱和多酚可以降低 HER2 以及 MMP 的表达。本研究综述了 40 多种针对肝癌和乳腺癌具有特定分子靶点的植物生物碱和多酚。其中,氧化苦参碱、毛蕊花碱、胡椒碱、索拉马金碱和布鲁金碱由于副作用较小,目前正在进行临床试验,被认为是有效的抗癌药物。由于对抗癌化合物进行了大量研究,因此有必要收集数据,以便进入临床试验的第四阶段,控制肝癌和乳腺癌的发病率。
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引用次数: 0
Curcumin and its Analogues in Oral Squamous Cell Carcinoma: State-of-the-art and Therapeutic Potential. 姜黄素及其类似物在口腔鳞状细胞癌中的应用:最新进展与治疗潜力。
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-05-16 DOI: 10.2174/0118715206297840240510063330
Valentina Schiavoni, Monica Emanuelli, Davide Sartini, Eleonora Salvolini, Valentina Pozzi, Roberto Campagna

Oral Squamous Cell Carcinoma (OSCC) is the most common cancer arising from squamous epithelium in the oral cavity and is characterized by high aggressiveness and metastatic potential, which together with a late diagnosis results in a 5-year survival rate of only 50% of patients. The therapeutic options for OSCC management are limited and largely influenced by the cancer stage. While radical surgery can be curative in early stage of disease, most cases require adjuvant therapies, including chemotherapy and radiotherapy which, however, often achieve poor curative rates and are associated with important negative effects. Therefore, there is an urgent need to discover new alternative treatment strategies to improve patients' outcomes. Several medicinal herbs are being studied for their preventive or therapeutic effect in several diseases, including cancer. In particular, the Indian spice curcumin, largely used in oriental countries, has been studied as a chemopreventive or adjuvant agent for different malignancies. Indeed, curcumin is characterized by important biological properties, including antioxidant, anti-inflammatory, and anticancer effects, which could also be exploited in OSCC. However, due to its limited bioavailability and poor aqueous solubility, this review is focused on studies designing new synthetic analogues and developing novel types of curcumin delivery systems to improve its pharmacokinetic and biological properties. Thus, this review analyses the potential therapeutic role of curcumin in OSCC by providing an overview of current in vitro and in vivo studies demonstrating the beneficial effects of curcumin and its analogues in OSCC.

口腔鳞状细胞癌(OSCC)是口腔鳞状上皮中最常见的癌症,具有高度侵袭性和转移性,加上诊断较晚,导致患者的 5 年生存率仅为 50%。OSCC 的治疗方案有限,且主要受癌症分期的影响。虽然根治性手术可以治愈早期病例,但大多数病例都需要辅助治疗,包括化疗和放疗,但这些疗法的治愈率往往很低,而且会产生重要的负面影响。因此,迫切需要发现新的替代治疗策略,以改善患者的治疗效果。目前正在研究几种药草对包括癌症在内的几种疾病的预防或治疗效果。特别是在东方国家广泛使用的印度香料姜黄素,已被研究用作不同恶性肿瘤的化学预防或辅助药物。事实上,姜黄素具有重要的生物特性,包括抗氧化、抗炎和抗癌作用,这些特性也可用于治疗 OSCC。然而,由于姜黄素的生物利用度有限且水溶性较差,本综述主要关注设计新的合成类似物和开发新型姜黄素给药系统的研究,以改善其药代动力学和生物特性。因此,本综述通过概述目前证明姜黄素及其类似物对 OSCC 有益的体外和体内研究,分析了姜黄素在 OSCC 中的潜在治疗作用。
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引用次数: 0
Ionic Liquids Immobilized Synthesis of New Xanthenes Derivatives and their Antiproliferative, Molecular Docking, and Morphological Studies 离子液体固定化合成新的氧杂蒽衍生物及其抗增殖、分子对接和形态学研究
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-30 DOI: 10.2174/0118715206299407240324110505
Rafat M. Mohareb, Rehab A. Ibrahim, Fatma O. Al Farouk, Ensaf S. Alwan
Background:: Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry. Objective:: This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents. Method:: The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 synthesized new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst. Results:: Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions. Conclusion:: The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.
背景::氧杂蒽和苯并氧杂蒽是有机化学和药物化学中非常有价值的化合物。研究发现,氧杂蒽衍生物在药物化学中有许多应用。研究目的本研究旨在探索具有不同取代基的氧杂蒽衍生物的合成,并发现其用作抗癌剂的可能性。方法:这项工作的基本起始化合物是 2,3-二氢-1H-氧杂蒽-1-酮(3),它是由环己-1,3-二酮和 2-羟基苯甲醛反应合成的。化合物 3 基于氧杂蒽核合成了新的噻吩、嘧啶、异噁唑和噻唑衍生物。通过进一步的杂环化反应,得到了融合的呫吨衍生物。本研究中的多组分反应是在溶剂存在的情况下,在 Et3N 催化下和在无溶剂离子液体固定催化剂中进行的。结果测定了新合成化合物对癌细胞株的细胞毒性,结果表明许多化合物具有很强的抑制作用。结论研究了合成化合物对六种选定癌细胞株的抗增殖活性。杂环的性质和取代基团的变化对测试化合物的抑制作用有很高的影响。
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引用次数: 0
Improving Tamoxifen Performance in Inducing Apoptosis and Hepatoprotection by Loading on a Dual Nanomagnetic Targeting System 通过在双重纳米磁性靶向系统上加载他莫昔芬,提高其诱导细胞凋亡和保护肝脏的性能
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-30 DOI: 10.2174/0118715206289666240423091244
Yanfang Zhao, Wanbao Ding, Peixian Zhang, Lei Deng, Yi Long, Jiuqin Lu, Fereshteh Shiri, Mostafa Heidari Majd
Background: Although tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds to estrogen receptors, it affects other estrogen-producing tissues due to passive diffusion and non-differentiation of normal and cancerous cells and leads to side effects. Methods: The problems expressed about tamoxifen (TMX) encouraged us to design a new drug delivery system based on magnetic nanoparticles (MNPs) to simultaneously target two receptors on cancer cells through folic acid (FA) and hyaluronic acid (HA) groups. The mediator of binding of two targeting agents to MNPs is a polymer linker, including dopamine, polyethylene glycol, and terminal amine (DPN). Results: Zeta potential, dynamic light scattering (DLS), and Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has a suitable size of ~105 nm and a surface charge of -41 mV, and therefore, it can be a suitable option for carrying TMX and increasing its solubility. The cytotoxic test showed that the highest concentration of MNPs-DPN-HA-FA-TMX decreased cell viability to about 11% after 72 h of exposure compared to the control. While the protective effect of modified MNPs on normal cells was evident, unlike tamoxifen, the survival rate of liver cells, even after 180 min of treatment, was not significantly different from the control group. The protective effect of MNPs was also confirmed by examining the amount of malondialdehyde, and no significant difference was observed in the amount of lipid peroxidation caused by modified MNPs compared to the control. Flow cytometry proved that TMX can induce apoptosis by targeting MNPs. Real-time PCR showed that the modified MNPs activated the intrinsic and extrinsic mitochondrial pathways of apoptosis, so the Bak1/Bclx ratio for MNPs-DPN-HA-FA-TMX and free TMX was 70.82 and 0.38, respectively. Also, the expression of the caspase-3 gene increased 430 times compared to the control. On the other hand, only TNF gene expression, which is responsible for metastasis in some tumors, was decreased by both free TMX and MNPs-DPN-HA-FA-TMX. Finally, molecular docking proved that MNPs-DPN-HA-FA-TMX could provide a very stable interaction with both CD44 and folate receptors, induce apoptosis in cancer cells, and reduce hepatotoxicity. Conclusion: All the results showed that MNPs-DPN-HA-FA-TMX can show good affinity to cancer cells using targeting agents and induce apoptosis in metastatic breast ductal carcinoma T-47D cell lines. Also, the protective effects of MNPs on hepatocytes are quite evident, and they can reduce the side effects of TMX.
背景:他莫昔芬(TMX)虽然属于选择性雌激素受体调节剂(SERMs),可选择性地与雌激素受体结合,但由于被动扩散和正常细胞与癌细胞的不分化作用,会影响其他产生雌激素的组织,导致副作用。方法:关于他莫昔芬(TMX)的问题促使我们设计了一种基于磁性纳米颗粒(MNPs)的新型给药系统,通过叶酸(FA)和透明质酸(HA)基团同时靶向癌细胞上的两种受体。两种靶向药物与 MNPs 结合的介质是聚合物连接体,包括多巴胺、聚乙二醇和端胺(DPN)。结果Zeta电位、动态光散射(DLS)和场发射扫描电子显微镜(FESEM)方法证实,MNPs-DPN-HA-FA具有约105 nm的合适尺寸和-41 mV的表面电荷,因此是携带TMX并增加其溶解度的合适选择。细胞毒性测试表明,与对照组相比,最高浓度的 MNPs-DPN-HA-FA-TMX 在暴露 72 小时后,细胞活力下降了约 11%。虽然改性 MNPs 对正常细胞的保护作用明显,但与他莫昔芬不同的是,即使在处理 180 分钟后,肝细胞的存活率与对照组相比也没有显著差异。通过检测丙二醛的含量也证实了 MNPs 的保护作用,与对照组相比,改性 MNPs 引起的脂质过氧化量没有明显差异。流式细胞术证明,TMX 可通过靶向 MNPs 诱导细胞凋亡。实时 PCR 显示,修饰的 MNPs 激活了线粒体凋亡的内在和外在途径,因此 MNPs-DPN-HA-FA-TMX 和游离 TMX 的 Bak1/Bclx 比值分别为 70.82 和 0.38。此外,与对照组相比,Caspase-3 基因的表达量增加了 430 倍。另一方面,游离 TMX 和 MNPs-DPN-HA-FA-TMX 只降低了 TNF 基因的表达,而 TNF 基因是某些肿瘤转移的罪魁祸首。最后,分子对接证明,MNPs-DPN-HA-FA-TMX 可与 CD44 和叶酸受体产生非常稳定的相互作用,诱导癌细胞凋亡,并降低肝毒性。结论所有研究结果表明,MNPs-DPN-HA-FA-TMX 能利用靶向药剂与癌细胞产生良好的亲和力,并能诱导转移性乳腺导管癌 T-47D 细胞系凋亡。此外,MNPs 对肝细胞的保护作用也相当明显,并能减轻 TMX 的副作用。
{"title":"Improving Tamoxifen Performance in Inducing Apoptosis and Hepatoprotection by Loading on a Dual Nanomagnetic Targeting System","authors":"Yanfang Zhao, Wanbao Ding, Peixian Zhang, Lei Deng, Yi Long, Jiuqin Lu, Fereshteh Shiri, Mostafa Heidari Majd","doi":"10.2174/0118715206289666240423091244","DOIUrl":"https://doi.org/10.2174/0118715206289666240423091244","url":null,"abstract":"Background: Although tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds to estrogen receptors, it affects other estrogen-producing tissues due to passive diffusion and non-differentiation of normal and cancerous cells and leads to side effects. Methods: The problems expressed about tamoxifen (TMX) encouraged us to design a new drug delivery system based on magnetic nanoparticles (MNPs) to simultaneously target two receptors on cancer cells through folic acid (FA) and hyaluronic acid (HA) groups. The mediator of binding of two targeting agents to MNPs is a polymer linker, including dopamine, polyethylene glycol, and terminal amine (DPN). Results: Zeta potential, dynamic light scattering (DLS), and Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has a suitable size of ~105 nm and a surface charge of -41 mV, and therefore, it can be a suitable option for carrying TMX and increasing its solubility. The cytotoxic test showed that the highest concentration of MNPs-DPN-HA-FA-TMX decreased cell viability to about 11% after 72 h of exposure compared to the control. While the protective effect of modified MNPs on normal cells was evident, unlike tamoxifen, the survival rate of liver cells, even after 180 min of treatment, was not significantly different from the control group. The protective effect of MNPs was also confirmed by examining the amount of malondialdehyde, and no significant difference was observed in the amount of lipid peroxidation caused by modified MNPs compared to the control. Flow cytometry proved that TMX can induce apoptosis by targeting MNPs. Real-time PCR showed that the modified MNPs activated the intrinsic and extrinsic mitochondrial pathways of apoptosis, so the Bak1/Bclx ratio for MNPs-DPN-HA-FA-TMX and free TMX was 70.82 and 0.38, respectively. Also, the expression of the caspase-3 gene increased 430 times compared to the control. On the other hand, only TNF gene expression, which is responsible for metastasis in some tumors, was decreased by both free TMX and MNPs-DPN-HA-FA-TMX. Finally, molecular docking proved that MNPs-DPN-HA-FA-TMX could provide a very stable interaction with both CD44 and folate receptors, induce apoptosis in cancer cells, and reduce hepatotoxicity. Conclusion: All the results showed that MNPs-DPN-HA-FA-TMX can show good affinity to cancer cells using targeting agents and induce apoptosis in metastatic breast ductal carcinoma T-47D cell lines. Also, the protective effects of MNPs on hepatocytes are quite evident, and they can reduce the side effects of TMX.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"21 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cerium Oxide Nanoparticles Synthesis Using Alhagi Maurorum Leaf Extract and Evaluation of Their Cytotoxic Effect on Breast Cancer Cell Lines and Antibacterial Effects 利用 Alhagi Maurorum 叶提取物合成纳米氧化铈颗粒并评估其对乳腺癌细胞株的细胞毒性作用和抗菌效果
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-30 DOI: 10.2174/0118715206296523240424072939
Sayedeh Azimeh Hosseini, Mehrdad Khatami, Amirkian Asadollahi, Hajar Yaghoobi
Introduction: Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated. Method: Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software. Results: The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria. Conclusion: These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.
引言这种方法的基础是利用天然材料,如植物、真菌和细菌,而不是有害且昂贵的化学还原剂来获得纳米粒子。本研究利用 Alhagi maurorum 提取物制备了 CeO2NPs,并对其抗癌和抗菌活性进行了评估。研究方法根据之前描述的方法制备 Alhagi maurorum 提取物,并用该提取物的盐合成 CeO2NPs。利用透射电子显微镜 (TEM)、扫描电子显微镜 (SEM) 和 X 射线衍射 (XRD) 技术对合成的纳米粒子进行了表征。纳米颗粒的抗菌和细胞毒性作用分别通过 MIC、MBC 和 MTT 试验进行了测定。结果采用 Prism 软件进行单因素方差分析(ANOVA)。结果乳腺癌细胞株的 MTT 试验表明,CeO2NPs 对细胞株的细胞毒性作用与浓度有关。此外,这种纳米粒子对革兰氏阳性菌更有效。结论这些纳米粒子除了用于抗癌治疗外,还可用作低浓度特异性靶向癌症给药系统。它还可用于生物和医药领域,如天然食品保鲜和伤口包扎。
{"title":"Cerium Oxide Nanoparticles Synthesis Using Alhagi Maurorum Leaf Extract and Evaluation of Their Cytotoxic Effect on Breast Cancer Cell Lines and Antibacterial Effects","authors":"Sayedeh Azimeh Hosseini, Mehrdad Khatami, Amirkian Asadollahi, Hajar Yaghoobi","doi":"10.2174/0118715206296523240424072939","DOIUrl":"https://doi.org/10.2174/0118715206296523240424072939","url":null,"abstract":"Introduction: Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated. Method: Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software. Results: The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria. Conclusion: These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"14 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biosynthesis and Anticancer Activity of Genistein Glycoside Derivatives 染料木苷衍生物的生物合成与抗癌活性
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-19 DOI: 10.2174/0118715206299272240409043726
Xing Zheng, Jun Zhang, Shun Liu, Yingzi Yu, Qingying Peng, Yaling Peng, Xu Yao, Xingxing Peng, Jing Zhou
: As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein’s clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.
:作为一种有益的天然类黄酮,染料木素通过调节多个靶点和信号通路,如抗癌、抗氧化、抗菌、抗炎、抗真菌、抗病毒、螯合铁、抗肥胖、抗糖尿病和抗高血压等,显示出广泛的生物学功能。在 2023 年 12 月底之前,我们使用适当的关键词对 PubMed/Medline 和 Web of Science 进行了检索。尽管染料木素具有许多潜在的益处,但由于其结构的原因,染料木素的临床应用受到亲水性低、溶解性差和生物利用度不理想的限制。这些难题可以通过将染料木素转化为糖苷来解决。活性小分子的糖基化可提高其溶解性、稳定性和生物活性。近年来,人们对糖类共轭物的合成、性质和抗癌活性进行了广泛的研究。以往的综述主要讨论了染料木素的生物活性,对染料木素苷衍生物的生物合成及其抗癌活性的结构-活性关系进行了少量总结。因此,我们总结了最近在染料木苷糖基化的生物合成方面取得的进展,并从结构-活性关系的角度讨论了染料木苷衍生物的抗肿瘤活性,这可能会为染料木苷衍生物的进一步开发提供重要信息。
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引用次数: 0
The Development of Organotin(IV) N-Ethyl-N-Benzyldithiocarbamate Complexes: A Study on Their Synthesis, Characterization, and Cytocidal Effects on A549 Cell Line 有机锡(IV)N-乙基-N-苄基二硫代氨基甲酸酯配合物的开发:有机锡(IV)N-乙基-N-苄基二硫代氨基甲酸络合物的开发:关于其合成、表征及其对 A549 细胞系杀细胞作用的研究
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-17 DOI: 10.2174/0118715206309421240402093335
Nurul Amalina Abd Aziz, Normah Awang, Nurul Farahana Kamaludin, Nur Najmi Mohamad Anuar, Asmah Hamid, Kok Meng Chan, Suhana Arshad
Background: Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research. background: Organotin(IV) compounds exhibit potent cytotoxicity through two primary mechanisms: binding to DNA via external phosphate groups and disrupting internal phospholipid metabolism, similarly to the mechanism of action of cisplatin. Additionally, the distinct stereoelectronic properties of these compounds endow them with exceptional therapeutic potential. Method: The two ONBDC derivatives – ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) – were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay. Results: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 μM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 μM). method: The compound was synthesized by using the in-situ method. Then, we used the elemental and spectroscopies analysis to characterize the compound. Subsequently, the cytotoxic potential of this compound is screened by using MTT assay. Conclusion: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.
背景:二硫代氨基甲酸有机锡(IV)复合物在药物化学中非常重要,由于其独特的性质可增强靶向递送,因此在靶向癌细胞方面具有潜力。本研究旨在合成和表征有机锡(IV)N-乙基-N-苄基二硫代氨基甲酸盐复合物(ONBDCs),并评估其对 A549 细胞(常用作人类肺癌研究的模型)的细胞毒性。 背景:有机锡(IV)化合物是药物化学中的重要成分:有机锡(IV)化合物通过两种主要机制表现出强大的细胞毒性:通过外部磷酸基团与 DNA 结合,以及破坏内部磷脂代谢,这与顺铂的作用机制类似。此外,这些化合物独特的立体电子学特性赋予了它们非凡的治疗潜力。研究方法两种 ONBDC 衍生物--ONBDC 1(二甲基锡(IV)N-乙基-N-苄基二硫代氨基甲酸酯)和 ONBDC 2(三苯基锡(IV)N-乙基-N-苄基二硫代氨基甲酸酯)--是通过氯化锡(IV)与 N-乙基苄胺在二硫化碳存在下的反应合成的。研究人员采用了一系列分析技术,包括元素分析、红外光谱、核磁共振光谱、紫外可见光谱、TGA/DTA 分析和 X 射线晶体学,对这些化合物进行了全面的表征。采用 MTT 法评估了 ONBDCs 对 A549 细胞的细胞毒性作用。结果:成功合成了这两种化合物,并通过元素分析和光谱分析对其进行了表征。MTT 试验显示,ONBDC 2 对 A549 细胞具有显著的细胞毒性,IC50 值为 0.52 μM。此外,与市售化疗药物顺铂(IC50:32 μM)相比,ONBDC 2 对 A549 细胞株的细胞毒性活性明显更高:采用原位法合成了该化合物。然后,我们利用元素分析和光谱分析对化合物进行了表征。随后,利用 MTT 试验筛选了该化合物的细胞毒性潜力。结论因此,研究表明 ONBDC 2 具有重要的抗癌特性,应将其作为改良和专门治疗癌症的首选药物进行进一步研究。
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引用次数: 0
Monochasma Savatieri Aqueous Extract inhibits Human Breast Cancer Cell Line Migration and Adhesion Without Generating Toxicity Monochasma Savatieri 水提取物可抑制人类乳腺癌细胞株的迁移和粘附,且不会产生毒性
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-17 DOI: 10.2174/0118715206287870240408031843
Lin Tan, Juan C. Solis-Sainz
Background: Monochasma savatieri, is a rare and endangered plant used to treat cancer in Chinese traditional medicine. Objective: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory, and anti-adhesion effects on breast cancer cells. objective: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory and anti-adhesion effects on breast cancer cells. Methods: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet (CV) staining, wound-healing, and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Immunofluorescent assays confirmed caveolin-1 expression in MDA-MB-231 cells. method: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet staining, wound-healing and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Caveolin-1 expression in MDA-MB-231 cells was confirmed by immunofluorescent assays. Results: Survival and cell cycle of MCF7 and MDA-MB-231 cells were not modified by doses up to 500 μg/mL of the extract. The extract inhibited cell migration and adhesion of MDA-MB-231 cells. When cells were exposed to the extract, there was a slight decrease in protein expression of factors related to epithelial-to-mesenchymal transition (snail and vimentin) and a strong decrease in the expression of the oncogenic membrane protein caveolin- 1. Furthermore, the levels of phosphorylated Erk and Akt were also decreased. The content of acteoside, a phenylpropanoid glycoside with reported anti-cancer activity present in M. savatieri, was almost 5 times as much as isoacteoside. Conclusion: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exhibited anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects. conclusion: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exerted anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects.
背景介绍野漆树(Monochasma savatieri)是一种罕见的濒危植物,在中国传统医学中被用来治疗癌症。研究目的通过测定蝙蝠蛾水提取物对乳腺癌细胞的细胞毒性、抗迁移和抗粘附作用,评估其抗癌活性:通过测定 M. savatieri 水提取物对乳腺癌细胞的细胞毒性、抗迁移和抗粘附作用,评估其抗癌活性。研究方法在 MCF7 和 MDA-MB-231 细胞中,通过水晶紫(CV)染色、伤口愈合、透孔试验和流式细胞术评估细胞活力、迁移、粘附、圆周率和细胞周期。MDA-MB-231细胞中的Caveolin-1、蜗牛、波形蛋白以及活化的Erk和Akt的表达是通过Western印迹法测定的。免疫荧光检测证实了洞穴素-1 在 MDA-MB-231 细胞中的表达:在 MCF7 和 MDA-MB-231 细胞中,通过水晶紫染色、伤口愈合和透孔试验以及流式细胞术评估细胞活力、迁移、粘附、圆周率和细胞周期。MDA-MB-231 细胞中的 Caveolin-1、蜗牛、波形蛋白以及活化的 Erk 和 Akt 的表达是通过 Western 印迹法测定的。免疫荧光试验证实了 Caveolin-1 在 MDA-MB-231 细胞中的表达。结果剂量高达 500 μg/mL 的提取物不会改变 MCF7 和 MDA-MB-231 细胞的存活率和细胞周期。提取物抑制了 MDA-MB-231 细胞的迁移和粘附。当细胞暴露于萃取物时,上皮细胞向间质转化相关因子(蜗牛和波形蛋白)的蛋白表达量略有下降,而致癌膜蛋白洞穴素-1的表达量则大幅下降。 此外,磷酸化的Erk和Akt的水平也有所下降。据报道,M. savatieri 中含有一种具有抗癌活性的苯基丙酮甙--肌苷,其含量几乎是异肌苷的 5 倍。结论M. savatieri 具有抗癌活性,但不会对乳腺癌细胞产生细胞毒性。该提取物通过调节 Erk 和 Akt 信号通路以及 caveolin-1 的表达,对乳腺癌细胞具有抗迁移和抗粘附作用。此外,M. savatieri 中的肌动球蛋白苷可能是产生这些效果的原因:M. savatieri具有抗癌活性,但不会对乳腺癌细胞产生细胞毒性。该提取物通过调节 Erk 和 Akt 信号通路以及洞穴素-1 的表达,对乳腺癌细胞产生抗迁移和抗粘附作用。此外,M. savatieri 中的肌动球蛋白苷可能是产生这些作用的原因。
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引用次数: 0
Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice 姜黄素、生姜、丁香和苦杏仁的草药提取物对艾氏腹水癌挑战小鼠的抗肿瘤免疫和化疗预防作用
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-16 DOI: 10.2174/0118715206269038231203151111
Soha Gomaa, Mohamed Nassef, Randa El-Naggar, Ahmed Massoud, Mona El-Kholy
Background:: Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. Aim:: The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Methods: Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. Results:: EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. Conclusion:: To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.
背景由于其全身毒性,传统的肿瘤化疗正受到重视。草药疗法含有植物化学多酚衍生物,如姜黄素(Cur)、生姜(Gin)、丁香(Clov)和杏仁酸(Amyg),是抗癌疗法的众多补充和替代方法之一,在癌症化疗预防方面前景广阔,副作用较小。研究目的本研究旨在评估莪术、生姜、姜黄和艾米格的草药提取物对艾氏腹水癌(EAC)小鼠的抗肿瘤免疫力以及抗癌和化疗预防效果。方法通过流式细胞术检测 EAC 肿瘤细胞的凋亡率,分析了 Cur、Gin、Clov 和 Amyg 中草药提取物的体内化疗预防功效。此外,还研究了 EAC 挑战小鼠外周血(PB)中 EAC 细胞总数、脾脏细胞计数和白细胞计数及其差值相对百分比。结果与单用 PBS 治疗的 EAC 小鼠相比,用 Cur、Gin、Clov 和 Amyg 的草药提取物治疗的 EAC 小鼠的 EAC 肿瘤细胞数量明显减少,EAC 肿瘤细胞的凋亡率明显增加,血清中癌抗原 125(CA-125)的水平显著下降,脾脏细胞数量明显增加。此外,数据还显示,在接受 Cur 和 Amyg 治疗的 EAC 挑食小鼠中,白细胞总数及其相对于嗜酸性粒细胞、中性粒细胞、单核细胞和淋巴细胞百分比的差异变化不明显,但在注射 Gin 和 Clov 的 EAC 挑食小鼠中,这些参数与单独接受 PBS 治疗的 EAC 挑食小鼠相比明显增加。结论总之,Cur、Gin、Clov 和 Amyg 的中草药提取物可能具有抗肿瘤免疫和抗癌功效,并有可能降低癌症常规化疗的耐药性,以较低的不良反应发挥癌症化疗保护作用。有必要开展进一步研究,以确定该疗法对不同组织和器官的毒性,并将该疗法的生物医学用途与诊断和治疗方法联系起来。
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引用次数: 0
Primary Pulmonary Lymphoepithelioma-like Carcinoma: A Case Report Utilizing Camrelizumab and Anlotinib for Prolonged Survival 原发性肺淋巴上皮瘤样癌症:利用康瑞珠单抗和安罗替尼延长生存期的病例报告
IF 2.8 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-04-16 DOI: 10.2174/0118715206294031240404071838
ShuangYi Lei, ShanShan Tian, SongMei Lu, Zhou Qing, JianLin Long, LuChun Li, Dan Yang
Background: Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months. Case Presentation: Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib. Result: This resulted in a progression-free survival of over 26 months without significant toxic side effects. Conclusion: Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.
背景:原发性肺淋巴上皮细胞瘤样癌症(PPLELC)是一种罕见的癌症,至今尚未确立标准治疗方法。晚期肺淋巴上皮细胞瘤患者一般预后较差,总生存期为 22.7 个月。病例介绍:我们在此报告一例晚期原发性肺淋巴上皮瘤样癌患者。最初,患者接受了一线化疗(GP)和二线化疗(DP),虽然暂时缓解了病情,但造成了不同程度的骨髓抑制。当病情再次进展时,我们采用了坎瑞珠单抗联合安罗替尼的三线治疗。治疗结果无进展生存期超过26个月,且无明显毒副作用。结论我们的研究结果表明,联合使用坎瑞珠单抗和安罗替尼可以延长晚期PPLELC患者的无进展生存期。
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引用次数: 0
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Anti-cancer agents in medicinal chemistry
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