Imidazoles

咪唑
  • 文章类型: Journal Article
    An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).
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  • 文章类型: Journal Article
    在这项研究中,通过外延生长法合成了混合骨架材料ZIF-8@ZIF-67,然后将其用作通过共沉淀法包封荧光假单胞菌脂肪酶(PFL)的载体,从而制备固定化脂肪酶(PFL@ZIF-8@ZIF-67)。随后,进一步用戊二醛处理以提高蛋白质固定化率。在最佳固定条件下,PFL@ZIF-8@ZIF-67的比水解活性是游离PFL的20.4倍。通过扫描电子显微镜(SEM)对所制备的生物催化剂进行了表征和分析,X射线衍射(XRD)傅里叶变换红外(FT-IR)。此外,与游离PFL相比,PFL@ZIF-8@ZIF-67在50°C下的热稳定性显着提高。在室温下放置7周后,PFL@ZIF-8@ZIF-67保留了78%的酯交换活性,而游离酶仅为29%。最后,将PFL@ZIF-8@ZIF-67应用于无溶剂体系中的乙酸金花酯制剂,反应3h后,乙酸金花酯的收率达到99%。重复10次之后,PFL@ZIF-8@ZIF-67和游离PFL催化的乙酸金花酯的收率分别为80%和43%,分别。
    In this study, hybrid skeleton material ZIF-8@ZIF-67 was synthesized by the epitaxial growth method and then was utilized as a carrier for encapsulating Pseudomonas fluorescens lipase (PFL) through the co-precipitation method, resulting in the preparation of immobilized lipase (PFL@ZIF-8@ZIF-67). Subsequently, it was further treated with glutaraldehyde to improve protein immobilization yield. Under optimal immobilization conditions, the specific hydrolytic activity of PFL@ZIF-8@ZIF-67 was 20.4 times higher than that of the free PFL. The prepared biocatalyst was characterized and analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). Additionally, the thermal stability of PFL@ZIF-8@ZIF-67 at 50 °C was significantly improved compared to the free PFL. After 7 weeks at room temperature, PFL@ZIF-8@ZIF-67 retained 78% of the transesterification activity, while the free enzyme was only 29%. Finally, PFL@ZIF-8@ZIF-67 was applied to the neryl acetate preparation in a solvent-free system, and the yield of neryl acetate reached 99% after 3 h of reaction. After 10 repetitions, the yields of neryl acetate catalyzed by PFL@ZIF-8@ZIF-67 and the free PFL were 80% and 43%, respectively.
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  • 文章类型: Journal Article
    这项研究旨在创新一种基于纳米酶的治疗策略,该策略将聚集诱导的发射(AIE)光敏剂与铜纳米酶相结合。这种方法旨在解决细菌感染中经常出现的缺氧状况,旨在通过确保足够的氧气供应来产生活性氧(ROS)来提高光动力疗法(PDT)的有效性。
    我们的方法涉及二羟基三苯基乙烯基吡啶(DHTPY)-Cu@唑来膦酸(ZOL)纳米酶颗粒的合成。我们最初合成了DHTPY,然后将其与铜纳米酶结合形成DHTPY-Cu@ZOL复合材料。纳米酶的大小,形态学,使用各种技术表征化学性质,包括动态光散射,透射电子显微镜,和X射线光电子能谱。我们进行了一系列的体外和体内测试,以评估光动力,抗菌,DHTPY-Cu@ZOL纳米酶的伤口愈合特性,包括它们的氧气产生能力,ROS生产,和对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌效果。
    DHTPY-Cu@ZOL表现出熟练的H2O2清除和氧气生成,在缺氧感染环境中增强PDT至关重要。我们的体外分析显示对MRSA有显著的抗菌作用,表明纳米酶有可能破坏细菌细胞膜。Further,使用MRSA感染伤口的糖尿病大鼠模型进行的体内研究表明,DHTPY-Cu@ZOL显着改善了伤口愈合并减少了细菌的存在,强调其作为慢性感染的非抗生素方法的功效。
    我们的研究表明,DHTPY-Cu@ZOL是一种非常有前途的对抗抗生素抗性微生物病原体和生物膜的方法。这些纳米酶颗粒的生物相容性和稳定性,加上其改善的PDT疗效使他们成为临床应用的有希望的候选人。
    UNASSIGNED: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.
    UNASSIGNED: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme\'s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
    UNASSIGNED: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes\' potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.
    UNASSIGNED: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.
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  • 文章类型: Journal Article
    唑类抗真菌药物通常用于治疗外阴阴道念珠菌病(VVC)。在现实世界中尚未系统地分析唑类药物的肾毒性和发育毒性。我们使用FDA不良事件报告系统(FAERS)来调查与咪唑治疗VVC相关的不良事件(AE)。使用OpenVigil2.1检索FAERS数据(从2004年第1季度到2022年第3季度),并根据监管活动医学词典(MedDRA)检索和标准化AE。在前10个系统器官类(SOC)中,所有四种药物都被发现患有肾脏和泌尿系统疾病以及怀孕。我们发现了重要的信号,包括克霉唑[膀胱移行细胞癌,(报告赔率比,ROR=291.66)],[胎儿死亡,(ROR=10.28)],酮康唑[肾性贫血(ROR=22.1)],[胎膜早破(ROR=22.9146.45,11,3)],咪康唑[血尿(ROR=19.03)],[新生儿败血症(ROR=123.71)],[自然流产(ROR=5.98)],益康唑[急性肾损伤(ROR=4.41)],[自然流产(ROR=19.62)]。我们还发现了未报告的新的不良反应。因此,当使用咪唑药物进行治疗时,有必要密切监测患者的肾功能,注意胎儿在怀孕期间的发育毒性,并意识到可能发生的潜在不良反应。
    Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient\'s renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.
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  • 文章类型: Journal Article
    病原菌一直对人类健康构成巨大挑战,创造对有效抗菌解决方案的关键需求。作为回应,酶-金属-有机骨架(MOF)复合材料已成为一类有前途的抗菌剂。本研究的重点是开发基于HZIF-8的酶-MOF复合材料,结合简单合成的优点,ZIF-8抗菌性能,溶菌酶水解,生物安全性高。通过一锅法,合成了核壳纳米粒子(HZIF-8)。该结构使得溶菌酶和乳铁蛋白能够在HZIF-8内有效固定,导致溶菌酶-乳铁蛋白@HZIF-8(LYZ-LF@HZIF-8)复合物的形成。在暴露于光照射下,HZIF-8本身具有抗菌性能。溶菌酶引发细菌肽聚糖和乳铁蛋白的降解协同增强了溶菌酶的抗菌作用。所有这些最终都有助于全面的抗菌活性。抗菌评估证明了LYZ-LF@HZIF-8复合材料的功效,以200μg/mL的低剂量有效根除1.5×106CFU/mL的金黄色葡萄球菌,以相同的细胞密度完全灭活400μg/mL的大肠杆菌。酶-MOF复合材料表现出显著和持久的抗菌功效,在体外没有明显的细胞毒性,从而揭示了在医疗和食品工业中应用的广阔前景。
    Pathogenic bacteria have consistently posed a formidable challenge to human health, creating the critical need for effective antibacterial solutions. In response, enzyme-metal-organic framework (MOF) composites have emerged as a promising class of antibacterial agents. This study focuses on the development of an enzyme-MOF composite based on HZIF-8, incorporating the advantages of simple synthesis, ZIF-8 antibacterial properties, lysozyme hydrolysis, and high biological safety. Through a one-pot method, core-shell nanoparticles (HZIF-8) were synthesized. This structure enables efficient immobilization of lysozyme and lactoferrin within the HZIF-8, resulting in the formation of the lysozyme-lactoferrin@HZIF-8 (LYZ-LF@HZIF-8) composite. Upon exposure to light irradiation, HZIF-8 itself possessed antibacterial properties. Lysozyme initiated the degradation of bacterial peptidoglycan and lactoferrin synergistically enhanced the antibacterial effect of lysozyme. All of the above ultimately contributed to comprehensive antibacterial activity. Antibacterial assessments demonstrated the efficacy of the LYZ-LF@HZIF-8 composite, effectively eradicating Staphylococcus aureus at a cell density of 1.5 × 106 CFU/mL with a low dosage of 200 μg/mL and completely inactivating Escherichia coli at 400 μg/mL with the same cell density. The enzyme-MOF composite exhibited significant and durable antibacterial efficacy, with no apparent cytotoxicity in vitro, thereby unveiling expansive prospects for applications in the medical and food industries.
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  • 文章类型: Journal Article
    这项研究通过使用沸石咪唑酯骨架8(ZIF-8)作为支架封装吲哚菁绿(ICG)和紫杉醇(Tax)来利用纳米技术。本研究旨在探讨ZIF-8@ICG@Tax纳米粒子(NPs)在非小细胞肺癌(NSCLC)治疗中的化学光热治疗潜力。通过基于静电相互作用的自组装进行“一体化”治疗ZIF-8@ICG@TaxNPs。首先,光热效应,稳定性,pH响应性,药物释放,通过体外测试评估ZIF-8@ICG@Tax的血液相容性。此外,通过体内试验评估ZIF-8@ICG@Tax的肝和肾毒性.此外,在体外和体内研究了这些纳米颗粒的抗癌作用。已成功合成了均匀稳定的化学光热ZIF-8@ICG@TaxNPs,并具有出色的药物释放能力。此外,ZIF-8@ICG@TaxNPs显示出显着的反应性,这取决于肿瘤微环境中的pH值和NIR照射,允许靶向药物递送和控制药物释放。NIR照射可以增强肿瘤细胞对ZIF-8@ICG@Tax摄取的反应,从而促进体内外抗肿瘤生长。ZIF-8@ICG@Tax和NIR辐照与它们各自的组分相比已显示出显著的协同抗肿瘤生长特性。这种新型的治疗-光热化学NPs作为NSCLC的可行治疗选择具有巨大的潜力。
    This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An \"all-in-one\" theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC.
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  • 文章类型: Journal Article
    冬凌草甲素(Ori)是一种天然存在的二萜物质,主要存在于中国药用植物冬凌草中。以前发现它具有有趣的生物学特性;然而,从血浆中的快速清除和在水中的有限溶解度限制了其作为药物的使用。几种金属有机框架(MOFs),有大的表面和大的毛孔,最近被认为是有前途的药物转运蛋白。沸石咪唑酯骨架-8(ZIF-8),由2-甲基咪唑和锌离子组成的MOF形式,在生理中性条件下结构稳定,而它可以在低pH值下降解,例如在肿瘤细胞中。在这里,纳米药物递送系统,Ori@ZIF-8被成功地设计用于包封和运输冬凌草甲素到肿瘤部位。制备的Ori@ZIF-8的载药量为26.78%,颗粒的平均尺寸为240.5nm。体外,Ori@ZIF-8的释放表现出酸敏感性,在中性条件下缓慢释放,在弱酸性条件下快速释放药物。根据体外抗肿瘤实验,Ori@ZIF-8比游离Ori产生更高的细胞毒性,并在A549癌细胞中诱导凋亡。总之,Ori@ZIF-8可能是一种潜在的pH响应载体,可以在肿瘤部位准确释放更多的冬凌酮。
    Oridonin (Ori) is a naturally existing diterpenoid substance that mainly exists in the Chinese medicinal plant Rabdosia rubescens. It was previously found to possess intriguing biological properties; however, the quick clearance from plasma and limited solubility in water restricts its use as a drug. Several metal-organic frameworks (MOFs), having big surfaces and large pores, have recently been considered promising drug transporters. The zeolitic imidazolate framework-8 (ZIF-8), a form of MOF consisting of 2-methylimidazole with zinc ions, is structurally stable under physiologically neutral conditions, while it can degrade at low pH values such as in tumor cells. Herein, a nanosized drug delivery system, Ori@ZIF-8, was successfully designed for encapsulating and transporting oridonin to the tumor site. The drug loading of the prepared Ori@ZIF-8 was 26.78%, and the particles\' mean size was 240.5 nm. In vitro, the release of Ori@ZIF-8 exhibited acid sensitivity, with a slow release under neutral conditions and rapid release of the drug under weakly acidic conditions. According to the in vitro anti-tumor experiments, Ori@ZIF-8 produced higher cytotoxicity than free Ori and induced apoptosis in A549 cancer cells. In conclusion, Ori@ZIF-8 could be a potential pH-responsive carrier to accurately release more oridonins at the tumor site.
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  • 文章类型: Journal Article
    由于微生物分解代谢与非生物吸附/氧化还原过程的耦合,生物-非生物混合系统最近已成为稳定有效去除持久性污染物的潜在技术。在这项研究中,BurkholderiavietnamensisC09V(B.V.C09V)成功地与沸石咪唑酯框架8(ZIF-8)整合,以使用聚乙烯醇/海藻酸钠(PVA/SA)作为培养基构建了最先进的生物-非生物系统。生物-非生物系统(PVA/SA-ZIF-8@B.V.C09V)能够在168小时内去除99.0%的2,4-DCP,远高于PVA/SA,PVA/SA-ZIF-8或PVA/SA@B.V.C09V(53.8%,72.6%和67.2%,分别)。电化学技术表明,PVA/SA的载体效应和ZIF-8的驱动效应共同加速了与酶促反应相关的电子转移过程。此外,定量PCR(Q-PCR)显示ZIF-8刺激B.V.C09V上调tfdB的表达,tfdC,CatA,和catC基因(2.40-,1.68-,1.58-,和1.23倍,分别),编码相关酶的代谢。此外,关键物理的影响,化学,通过Spearman相关分析,对PVA/SA-ZIF-8@B.V.C09V对2,4-DCP的去除作用和生物学特性进行了统计研究,以确定促进2,4-DCP协同去除的关键因素。总的来说,这项研究为水生环境中2,4-DCP的可持续修复创造了创新的新策略。
    Biotic-abiotic hybrid systems have recently emerged as a potential technique for stable and efficient removal of persistent contaminants due to coupling of microbial catabolic with abiotic adsorption/redox processes. In this study, Burkholderia vietnamensis C09V (B.V.C09V) was successfully integrated with a Zeolitic Imidazolate Framework-8 (ZIF-8) to construct a state-of-art biotic-abiotic system using polyvinyl alcohol/ sodium alginate (PVA/SA) as media. The biotic-abiotic system (PVA/SA-ZIF-8 @B.V.C09V) was able to remove 99.0 % of 2,4-DCP within 168 h, which was much higher than either PVA/SA, PVA/SA-ZIF-8 or PVA/SA@B.V.C09V (53.8 %, 72.6 % and 67.2 %, respectively). Electrochemical techniques demonstrated that the carrier effect of PVA/SA and the driving effect of ZIF-8 collectively accelerated electron transfer processes associated with enzymatic reactions. In addition, quantitative-PCR (Q-PCR) revealed that ZIF-8 stimulated B.V.C09V to up-regulate expression of tfdB, tfdC, catA, and catC genes (2.40-, 1.68-, 1.58-, and 1.23-fold, respectively), which encoded the metabolism of related enzymes. Furthermore, the effect of key physical, chemical, and biological properties of PVA/SA-ZIF-8 @B.V.C09V on 2,4-DCP removal were statistically investigated by Spearman correlation analysis to identify the key factors that promoted synergistic removal of 2,4-DCP. Overall, this study has created an innovative new strategy for the sustainable remediation of 2,4-DCP in aquatic environments.
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  • 文章类型: Journal Article
    提出了一种高效的PEC生物传感器,用于基于从CdTe量子点(CdTeQDs)到Au纳米颗粒(AuNPs)的激子能量转移的ATP检测,整合CRISPR/Cas12a反式切割活性和ZIF-67对ATP的特异性识别。CdTe量子点与AuNPs系统之间的激子能量传递起首被构建为光电化学(PEC)传感基底。然后,活化剂DNA,用于激活CRISPR/Cas12a,在ZIF-67的表面被吸收。在ATP存在的情况下,由于ZIF-67对ATP的更有效吸附,活化剂DNA被释放。释放的激活剂DNA激活CRISPR/Cas12a的反式切割活性,以降解电极上的ssDNA,导致光电流的恢复由于中断的能量转移。受益于ZIF-67对ATP的特异性识别和CRISPR/Cas12a调控的扩增策略,该传感器具有优异的特异性和高灵敏度。
    An efficient PEC biosensor is proposed for ATP detection based on exciton energy transfer from CdTe quantum dots (CdTe QDs) to Au nanoparticles (AuNPs), integrating CRISPR/Cas12a trans-cleavage activity and specific recognition of ZIF-67 to ATP. Exciton energy transfer between CdTe QDs and AuNPs system is firstly constructed as photoelectrochemical (PEC) sensing substrate. Then, the activator DNAs, used to activate CRISPR/Cas12a, are absorbed on the surface of ZIF-67. In the presence of ATP, the activator DNAs are released due to more efficient adsorption of ZIF-67 to ATP. The released activator DNA activates trans-cleavage activity of CRISPR/Cas12a to degrade ssDNA on the electrode, leading to the recovery of photocurrent due to the interrupted energy transfer. Benefiting from the specific recognition of ZIF-67 to ATP and CRISPR/Cas12a-modulated amplification strategy, the sensor is endowed with excellent specificity and high sensitivity.
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  • 文章类型: Journal Article
    RogersoninsC-F(1-4),四个前所未有的腺嘌呤-聚酮杂种,具有罕见的9H-咪唑并[2,1-i]嘌呤(1,N6-乙烯腺嘌呤)部分,是从与冬虫夏草相关的真菌中分离出来的,Clonostachysrogersoniana.它们的结构主要通过NMR实验阐明。1-4的绝对配置是通过改进的Mosher方法的组合分配的,化学降解,电子圆二色性(ECD)计算,和使用CuKα辐射的X射线晶体学。化合物3下调MDA-MB-231和A549细胞中PD-L1蛋白的表达,但对PD-L1编码基因CD274的mRNA转录没有检测到的影响。
    Rogersonins C-F (1-4), four unprecedented adenine-polyketide hybrids featuring a rare 9H-imidazo[2,1-i]purine (1,N6-ethenoadenine) moiety, were isolated from an Ophiocordyceps-associated fungus, Clonostachys rogersoniana. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 1-4 were assigned by a combination of the modified Mosher method, chemical degradation, electronic circular dichroism (ECD) calculations, and X-ray crystallography using Cu Kα radiation. Compound 3 downregulated the expression of PD-L1 protein in MDA-MB-231 and A549 cells, but did not show detectable effect on mRNA transcription of the PD-L1-encoding gene CD274.
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