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31.
目的 分析三氮唑席夫碱衍生物(LH-37)诱导人肝癌细胞(SMMC-7721细胞)自相残的形态特征。 方法 1×104/ml个SMMC-7721细胞,培养在含1×10-5 mol/L LH-37的培养液内24h、48h,巴氏、瑞氏染色分析细胞结构,免疫细胞化学方法观察激活型Caspase阳性细胞,透射电镜观察自相残细胞超微结构。 结果 常规显微镜下可见自相残的细胞表现为一个细胞被另一个细胞完全包裹,一些被邻近大细胞内在化的细胞由较大的囊泡包裹。LH-37作用SMMC-7721细胞48h,自相残细胞达5.23%,对照组为0.47%,大部分被包裹的小细胞表现为激活型Caspase-3阳性。LH-37作用24h,透射电镜下可见被大细胞包裹的小细胞呈现活细胞特征,至48h,被包裹的小细胞降解甚至只剩下残片。 结论 LH-37能够诱导人肝癌细胞自相残。 相似文献
32.
Ming Zhang Wen-Kui Sun Ting Wu Fei Chen Xiao-Yong Xu Xin Su Yi Shi 《Journal of thoracic disease》2014,6(2):99-108
Objective
The effectiveness of the combination therapy of triazole and echinocandin in treatment of invasive aspergillosis (IA) remains controversial. The objective of this systematic review was to assess the efficacy of combination therapy of triazole and echinocandin in treatment of IA.Methods
Relevant articles on the combination therapy of triazole and echinocandin in IA, including the animal studies and clinical studies from January 1966 to October 2013, were searched on Web of Science, PubMed and Cochrane Library. The prolongation of survival of the combination therapy of triazole and echinocandin in IA was performed as risk ratio (RR) with 95% confidence interval (95% CI).Results
Nine animal studies with a total of 1,582 animals and five clinical trials totaling 872 patients were included. The survival of the included animal studies with combination therapy was significantly prolonged compared with echinocandin alone [RR =2.26, (95% CI, 1.79-2.87; P<0.00001)], but no statistical difference compared with monotherapy of triazole [RR =1.19, (95% CI, 0.98-1.44; P=0.08)]. Of the four human cohort studies, two studies observed that the combination therapy of triazole and echinocandin was associated with a significant reduction in mortality compared with other treatments, and one study might be considered as a preferable therapy [HR =0.58, (95% CI, 0.3-1.14; P=0.117)]. While another study revealed that there was no significant difference among the combination therapy of triazole and echinocandin and either of the monotherapy. In the randomized clinical trial (RCT), of the 135 patients who received the combination therapy, 39 died, while 55 died out of 142 patients who received monotherapy (P=0.08, 95% CI, –21.4, 1.09) by week 12.Conclusions
The combination therapy of triazole and echinocandin in treating IA results in a trend towards improved overall survival in animals’ studies and clinical studies. Well-designed RCTs and further improved clinical trials are necessary to study the effectiveness of the combination therapy. 相似文献33.
The 6,6-dibromopenam (6) was treated with CH3MgBr and carbaldehyde 5 to afford the hydroxy compound 7, which was reacted with acetic anhydride to give acetoxy compound 8. The deacetobromination of 8 with zinc and acetic acid gave 6-exomethylenepenams, E-isomer 10 and Z-isomer 9, which was oxidized to sulfone 11 by m-CPBA. The p-methoxybenzyl compounds were deprotected by AlCl3 and neutralized to give the sodium salts 12, 13 and 14. 相似文献
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36.
Mariem Chaâbane Mohamed Koubaa Nejla Soudani Awatef Elwej Malek Grati Kamel Jamoussi 《Pharmaceutical biology》2017,55(1):1061-1073
Context: Nitraria retusa (Forssk.) Asch. (Nitrariaceae) is a medicinal plant which produces edible fruits whose antioxidant activity has been demonstrated.Objective: The current study elucidates the potential protective effect of N. retusa fruit aqueous extract against nephrotoxicity induced by penconazole, a triazole fungicide, in the kidney of adult rats.Materials and methods: Adult Wistar rats were exposed either to penconazole (67?mg/kg body weight), or to N. retusa extract (300?mg/kg body weight) or to their combination. Penconazole was administered by intra-peritoneal injection every 2 days from day 7 until day 15, the sacrifice day, while N. retusa extract was administered daily by gavage during 15 days. Oxidative stress parameters, kidney biomarkers and histopathological examination were determined.Results: Nitraria retusa extract administration to penconazole treated rats decreased kidney levels of malondialdehyde (?10%), hydrogen peroxide (?12%), protein carbonyls (PCOs, ?11%) and advanced oxidation protein products (AOPP, ?16%); antioxidant enzyme activities: catalase (?13%), superoxide dismutase (?8%) and glutathione peroxidase (GPx, ?14%), and the levels of non-enzymatic antioxidants: non-protein thiols (?9%), glutathione (?7%) and metallothionein (?12%). Furthermore, this plant extract prevented kidney biomarker changes by reducing plasma levels of creatinine, urea, uric acid and LDH and increasing those of ALP and GGT. Histopathological alterations induced by penconazole (glomeruli fragmentation, Bowman’s space enlargement, tubular epithelial cells necrosis and infiltration of inflammatory leucocytes) were attenuated following N. retusa administration.Discussion and conclusion: Our results indicated that N. retusa fruit extract had protective effects against penconazole-induced kidney injury, which could be attributed to its phenolic compounds. 相似文献
37.
The novel anti-tumor agents of 4-triazol-1,8-naphthalimides: synthesis, cytotoxicity, DNA intercalation and photocleavage 总被引:1,自引:0,他引:1
Li X Lin Y Wang Q Yuan Y Zhang H Qian X 《European journal of medicinal chemistry》2011,46(4):1274-1279
A novel series of 4-(4-phenyl-[1,2,3]-triazol-1-yl)-1,8-naphthalimide derivatives had been synthesized easily by employing “click reaction”. For anti-tumor activity in vitro, all the compounds were found to be more toxic against MCF-7 than Hela and 7721 cells. 4a, 4b and 4e Showed improved cytotoxic activity against MCF-7 cells over Amonafide, in particular compound 4a, with an IC50 could amount to 10−7 M. The UV-vis spectra and Circular Dichroism titration indicated that the compounds behaved as effective DNA-intercalating agents. The investigation of their photo-damaging ability illuminated that these compounds could damage DNA effectively into form II and even form III. 相似文献
38.
Doiron J Soultan AH Richard R Touré MM Picot N Richard R Cuperlović-Culf M Robichaud GA Touaibia M 《European journal of medicinal chemistry》2011,46(9):4010-4024
A series of bis- and mono-benzonitrile or phenyl analogues of letrozole 1, bearing (1,2,3 and 1,2,5)-triazole or imidazole, were synthesized and screened for their anti-aromatase activities. The unsubstituted 1,2,3-triazole 10a derivative displayed inhibitory activity comparable with that of the aromatase inhibitor, letrozole 1. Compound 10a, bearing a 1,2,3-triazole, is also 10000-times more tightly binding than the corresponding analogue 25 bearing a 1,2,5-triazole, which confirms the importance of a nitrogen atom at position 3 or 4 of the 5-membered ring needed for high activity. The effect on human epithelial adrenocortical carcinoma cell line (H295R) proliferation was also evaluated. The compound 10j (IC50 = 4.64 μM), a letrozole 1 analogue bearing para-cyanophenoxymethylene-1,2,3-triazole decreased proliferation rates of H295R cells by 76 and 99% in 24 and 72 h respectively. Computer calculations, using quantum ab initio structures, suggest a possible correlation between anti-aromatase activity and the distance between the nitrogen in position 3 or 4 of triazole nitrogen and the cyano group nitrogen. 相似文献
39.
Chai X Zhang J Cao Y Zou Y Wu Q Zhang D Jiang Y Sun Q 《European journal of medicinal chemistry》2011,46(7):3167-3176
In order to meet the urgent need for novel antifungal agents with improved activity and broader spectrum, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted trifluoromethyl phenyl)-piperazin-1-yl]-propan-2-ols were designed, synthesized and evaluated as antifungal agents. The MIC80 values indicate that the compounds 7a-7q, 8a-8d showed higher antifungal activities against Candida albicans than 5a-5i, 6a-6j. Moreover, the molecular model for the binding between compound 5a, 7a and the active site of CACYP51 was provided based on the computational docking results, and the structure-activity relationship was analyzed. 相似文献
40.
A series of 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1(2H)-ones was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, 2-propionyl-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one 4b was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED(50)) of 8.2 mg/kg, median toxicity dose (TD(50)) of 318.3 mg/kg, and the protective index (PI) of 39.0 which is much greater than the PI of the reference drugs phenytoin and carbamazepine. 相似文献