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91.
Hongyan Liu Xiaoming Qiang Qing Song Wei Li Yuxi He Chanyuan Ye Zhenghuai Tan Yong Deng 《Bioorganic & medicinal chemistry》2019,27(6):991-1001
A series of 4′-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (65.03% at 25.0?μM). Moreover, this representative compound also exhibited good antioxidant activity, biometal chelating ability and anti-neuroinflammatory activity in vitro. Furthermore, compound 8n displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 8n as promising candidate for further development of multi-functional drugs against AD. 相似文献
92.
Qianqian Liu Xia Li Yong-Sheng Bao Jingxin Lu Hua Li Zhizhen Huang Feiyan Liu 《Bioorganic & medicinal chemistry》2019,27(8):1489-1496
Deregulation of ceramide metabolism is a hallmark of human cancer. Ceramide analogues thereby represent a new class of anti-cancer agents. We aimed at developing effective and low toxic ceramide analogues and synthesized a new class of ceramide analogues starting from l-threonine. Several analogues exhibit potent cytotoxicity against human cancer cells in vitro with IC50 as low as 4.8?μM. These ceramide analogues decreased xIAP and Bcl-xL level and exhibited significant sensitization activity to overcome human cancer cell resistance to TRAIL, a cancer-selective agent that are being tested in human clinical trials. Furthermore, we determined that these ceramide analogues effectively suppress human cancer xenograft growth in vivo with no significant toxicity at the efficacious dose. Therefore, we have developed a simple and effective method to synthesize functional ceramide analogues using l-threonine as starting material and these analogues have the great potential to be further developed as anti-cancer agents in human cancer therapy. 相似文献
93.
S. Mnguni 《Biocontrol Science and Technology》2019,29(12):1146-1158
ABSTRACTEccritotarsus spp. are biological control agents that have been sourced from Brazil and Peru to control water hyacinth in South Africa. These agents have been released in over 30 sites and were thought to be the same species. The sequencing of mitochondrial DNA and interbreeding experiments have since confirmed the cryptic species to be separate species. The Brazilian population remains E. catarinensis while the Peruvian population is now E. eichhorniae. This paper assessed the mating behaviour of both species, to investigate behavioural traits that have resulted in reproductive isolation, which could have led to speciation. Mating choices in a form of no-choice, bi-choice and multi-choice tests were conducted within and between species in a 3:1, 2:1 and 1:1 sex ratio. The E. eichhorniae pair had more single and multiple copula incidences, higher average total copula duration and higher copula latency while the E.catarinensis♀×E.eichhorniae♂ pair had less single and multiple copula incidences, lower average total copula duration and lower copula latency. When the E.eichhorniae♀ and E.catarinensis♂ were given their respective choices, they only mated with conspecifics. However, when E.eichhorniae♀ are crossed with E.catarinensis♂ they do not produce offspring. These results suggest that interbreeding will be limited in South Africa. 相似文献
94.
以四氧化三铁为代表的医用磁性纳米材料具有独特的磁学性能、表面易功能化、良好的生物学相容性等特点,在纳米医学相关领域展现出巨大的应用前景,特别是近年来它作为可介导外场的智能材料,在材料设计和生物医学应用方面均取得了突破性的进展.鉴于此,本文围绕磁性氧化铁纳米材料的生物医学应用,着重介绍近年来其在磁共振影像探针、磁热和磁力效应的生物医学应用、诊疗一体化以及纳米酶催化等领域的研究进展,并对磁性纳米材料在生物医学领域未来的发展方向进行了展望. 相似文献
95.
微生态制剂(microbial ecological agents, MEA)是利用益生菌及其代谢产物而制成的一种药物制剂。MEA主要是通过补充有益的微生物来重建人体肠道内的菌群平衡,以治疗多种胃肠道疾病。现就近年来MEA在胃肠道中的作用机制,以及在防治炎症性肠病、与抗生素相关的腹泻、幽门螺杆菌感染和慢性肝病等疾病中的临床应用作一概述,为更好地开发和利用MEA治疗疾病奠定基础。 相似文献
96.
目的:利用喷雾干燥工艺制备芽孢杆菌dhs-330-021菌粉,并研究菌粉的活性及稳定性。方法:以脱脂乳、海藻糖、β-环糊精和谷氨酸钠为保护剂,采用喷雾干燥(条件为:进口温度100℃,出口温度50~60℃,进样速度2~4mL/min)制备芽孢杆菌菌粉,以喷干存活率和菌粉活菌数为指标,选择最佳制备条件。结果:获得喷干保护剂配方为脱脂乳10.0%、海藻糖6.0%、β-环糊精13.0%、谷氨酸钠15.0%,喷干存活率为65.9%,菌粉活菌数为1.38×109CFU/g,存放180 d后菌粉活菌数为1.03×10~9CFU/g。结论:喷雾干燥工艺可以用于芽孢杆菌dhs-330-021菌粉的制备,获得的菌粉稳定性较好。 相似文献
97.
Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted on a series (44 compounds) of diaryloxy-methano-phenanthrene derivatives as potent antitubercular agents. The best predictions were obtained with a CoMFA standard model (q (2)=0.625, r (2)=0.994) and with CoMSIA combined steric, electrostatic, and hydrophobic fields (q (2)=0.486, r (2)=0.986). Both models were validated by a test set of seven compounds and gave satisfactory predictive r (2) values of 0.999 and 0.745, respectively. CoMFA and CoMSIA contour maps were used to analyze the structural features of the ligands to account for the activity in terms of positively contributing physicochemical properties: steric, electrostatic, and hydrophobic fields. The information obtained from CoMFA and CoMSIA 3-D contour maps can be used for further design of phenanthrene-based analogs as anti-TB agents. The resulting contour maps, produced by the best CoMFA and CoMSIA models, were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction-field contour maps also showed a high level of internal consistency. This study suggests that introduction of bulky and highly electronegative groups on the basic amino side chain along with decreasing steric bulk and electronegativity on the phenanthrene ring might be suitable for designing better antitubercular agents. 相似文献
98.
Aref Shariati Soheil Vesal Amin Khoshbayan Parnian Goudarzi Davood Darban-Sarokhalil Shabnam Razavi Mojtaba Didehdar Zahra Chegini 《Journal of applied microbiology》2022,132(4):2531-2546
An important role has been recently reported for bacterial biofilm in the pathophysiology of chronic diseases, such as chronic rhinosinusitis (CRS). CRS, affecting sinonasal mucosa, is a persistent inflammatory condition with a high prevalence around the world. Although the exact pathological mechanism of this disease has not been elicited yet, biofilm formation is known to lead to a more significant symptom burden and major objective clinical indicators. The high prevalence of multidrug-resistant bacteria has severely restricted the application of antibiotics in recent years. Furthermore, systemic antibiotic therapy, on top of its insufficient concentration to eradicate bacteria in the sinonasal biofilm, often causes toxicity, antibiotic resistance, and an effect on the natural microbiota, in patients. Thus, coming up with alternative therapeutic options instead of systemic antibiotic therapy is emphasized in the treatment of bacterial biofilm in CRS patients. The use of topical antibiotic therapy and antibiotic eluting sinus stents that induce higher antibiotic concentration, and decrease side effects could be helpful. Besides, recent research recognized that various natural products, nitric oxide, and bacteriophage therapy, in addition to the hindered biofilm formation, could degrade the established bacterial biofilm. However, despite these improvements, new antibacterial agents and CRS biofilm interactions are complicated and need extensive research. Finally, most studies were performed in vitro, and more preclinical animal models and human studies are required to confirm the collected data. The present review is specifically discussing potential therapeutic strategies for the treatment of bacterial biofilm in CRS patients. 相似文献
99.
Human kinesin Eg5 is a potential inhibiting site for cancer chemotherapy. Blocking metaphase by binding foreign inhibitors with Eg5 eventually leads to apoptotic cell death. Here, we report the pyrazolopyrimidine derivates as potent inhibitors of Eg5 that prevents mitotic kinesin progression. IC50 values were evaluated against the motor domain of Eg5 using steady-state ATPase assay. To better understanding, we have performed molecular docking simulation. It reveals that the interactions of the proposed inhibitors with both the allosteric sites (helices α2, α3 and loopL5, and helices α4 & α6). Out of fifteen pyrazolopyrimidine derivates, three compounds (12, 25, and 27) have shown significant inhibition of Eg5. The synthesized compounds (12, 25, and 27) were tested for their in-vitro anticancer activity against cervical cancer cell line (HeLa). 相似文献
100.
《Bioorganic & medicinal chemistry letters》2020,30(10):127114
A lead compound with the (1,3,4-thiadiazol-2-yl)-acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC50 values of 1–5 μM on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC50 > 50 μM on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia. 相似文献