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41.
Following our efforts towards the synthesis of new potential inhibitors of Xanthine Dehydrogenase (XDH), we describe here a general method for the preparation of N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycines and N-(5-oxo-2,5-dihydro)pyrrol-3-yl glycine esters from glycine ethyl ester hydrochloride and various 4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylic acid esters and carbonitriles. 相似文献
42.
Daria Kupczyk Renata Studziska Szymon Baumgart Rafa Bilski Tomasz Kosmalski Renata Koodziejska Alina Wo
niak 《Molecules (Basel, Switzerland)》2021,26(9)
Tumors are currently more and more common all over the world; hence, attempts are being made to explain the biochemical processes underlying their development. The search for new therapeutic pathways, with particular emphasis on enzymatic activity and its modulation regulating the level of glucocorticosteroids, may contribute to the development and implementation of new therapeutic options in the treatment process. Our research focuses on understanding the role of 11β-HSD1 and 11β-HSD2 as factors involved in the differentiation and proliferation of neoplastic cells. In this work, we obtained the 9 novel N-tert-butyl substituted 2-aminothiazol-4(5H)-one (pseudothiohydantoin) derivatives, differing in the substituents at C-5 of the thiazole ring. The inhibitory activity and selectivity of the obtained derivatives in relation to two isoforms of 11β-HSD were evaluated. The highest inhibitory activity for 11β-HSD1 showed compound 3h, containing the cyclohexane substituent at the 5-position of the thiazole ring in the spiro system (82.5% at a conc. 10 µM). On the other hand, the derivative 3f with the phenyl substituent at C-5 showed the highest inhibition of 11β-HSD2 (53.57% at a conc. of 10 µM). A low selectivity in the inhibition of 11β-HSD2 was observed but, unlike 18β-glycyrrhetinic acid, these compounds were found to inhibit the activity of 11β-HSD2 to a greater extent than 11β-HSD1, which makes them attractive for further research on their anti-cancer activity. 相似文献
43.
Hun Ho Park Junseong Park Hye Joung Cho Jin-Kyoung Shim Ju Hyung Moon Eui Hyun Kim Jong Hee Chang Soo Youl Kim Seok-Gu Kang 《Molecules (Basel, Switzerland)》2021,26(2)
Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action. 相似文献
44.
Mohammed Hamed Alqarni Ahmed Ibrahim Foudah Magdy Mohamed Muharram Haritium Budurian Nikolaos E. Labrou 《Molecules (Basel, Switzerland)》2021,26(5)
The reactive adenosine derivative, adenosine 5′-O-[S-(4-hydroxy-2,3-dioxobutyl)]-thiophosphate (AMPS-HDB), contains a dicarbonyl group linked to the purine nucleotide at a position equivalent to the pyrophosphate region of NAD+. AMPS-HDB was used as a chemical label towards Candida boidinii formate dehydrogenase (CbFDH). AMPS-HDB reacts covalently with CbFDH, leading to complete inactivation of the enzyme activity. The inactivation kinetics of CbFDH fit the Kitz and Wilson model for time-dependent, irreversible inhibition (KD = 0.66 ± 0.15 mM, first order maximum rate constant k3 = 0.198 ± 0.06 min−1). NAD+ and NADH protects CbFDH from inactivation by AMPS-HDB, showing the specificity of the reaction. Molecular modelling studies revealed Arg174 as a candidate residue able to be modified by the dicarbonyl group of AMPS-HDB. Arg174 is a strictly conserved residue among FDHs and is located at the Rossmann fold, the common mononucleotide-binding motif of dehydrogenases. Arg174 was replaced by Asn, using site-directed mutagenesis. The mutant enzyme CbFDHArg174Asn was showed to be resistant to inactivation by AMPS-HDB, confirming that the guanidinium group of Arg174 is the target for AMPS-HDB. The CbFDHArg174Asn mutant enzyme exhibited substantial reduced affinity for NAD+ and lower thermostability. The results of the study underline the pivotal and multifunctional role of Arg174 in catalysis, coenzyme binding and structural stability of CbFDH. 相似文献
45.
粘红酵母处理味精废水的研究 总被引:4,自引:0,他引:4
对粘红酵母处理味精废水的条件进行研究。结果表明最佳处理条件为:进水COD浓度为10000mg/L,pH为6.16,发酵温度为32℃,发酵时间为72h,接种量为15%。该条件下可使味精废水COD的去除率达80.53%以上,利用发酵后的菌体,可提取单细胞蛋白,提取油脂,具有一定的应用潜力。 相似文献
46.
Emanuela Colombo Rosaria Pascente Daniela Triolo Claudia Bassani Anthea De Angelis Francesca Ruffini Linda Ottoboni Giancarlo Comi Gianvito Martino Cinthia Farina 《Molecules (Basel, Switzerland)》2020,25(22)
Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte–neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally, in vitro experiments with rat spinal neurons showed that laquinimod did not exert neuroprotection directly on the neuron but dampened astrocyte-induced neurodegeneration. Our findings indicate that fibroblast-derived human astrocytes represent a suitable model to study astrocyte–neuron crosstalk and demonstrate indirect, partial neuroprotective efficacy for laquinimod. 相似文献
47.
Xiaojia Guo Yuxue Liu Qian Wang Xueying Wang Qing Li Wujun Liu Zongbao K. Zhao 《Angewandte Chemie (International ed. in English)》2020,59(8):3143-3146
A non‐natural cofactor and formate driven system for reductive carboxylation of pyruvate is presented. A formate dehydrogenase (FDH) mutant, FDH*, that favors a non‐natural redox cofactor, nicotinamide cytosine dinucleotide (NCD), for generation of a dedicated reducing equivalent at the expense of formate were acquired. By coupling FDH* and NCD‐dependent malic enzyme (ME*), the successful utilization of formate is demonstrated as both CO2 source and electron donor for reductive carboxylation of pyruvate with a perfect stoichiometry between formate and malate. When 13C‐isotope‐labeled formate was used in in vitro trials, up to 53 % of malate had labeled carbon atom. Upon expression of FDH* and ME* in the model host E. coli, the engineered strain produced more malate in the presence of formate and NCD. This work provides an alternative and atom‐economic strategy for CO2 fixation where formate is used in lieu of CO2 and offers dedicated reducing power. 相似文献
48.
观测了冬眠前饲料中添加外源维生素C(Vc)对冬眠中华鳖稚鳖能量代谢的影响.结果发现外源Vc不能提高冬眠期间中华鳖的存活率(P=0.57).稚鳖个体在冬眠期间生长能的平均值为-0.15 kJ.d-1,该值与代谢耗能相当.鳖体蛋白、脂肪、水分和灰分质量分数w在冬眠前后无显著差异(P>0.05),外源Vc对鳖的体组成没有明显影响(P>0.05).冬眠8周后,肝脏线粒体细胞色素C氧化酶(COX)和肝脏乳酸锐氢酶(LDH)的活性显著下降(P<0.05).饲料外源Vc对肝脏线粒体蛋白含量、肝脏线粒体COX和LDH的活性均无影响(P>0.05). 相似文献
49.
从300多种土壤样品中进行筛选,最终得到10株可耐受300 g/L木糖的酵母菌株,且其木糖醇转化率超过64.0%.其中酵母菌株SB18在150 g/L木糖下的木糖醇转化率为68.5%,为相同条件下转化率最大的菌株,并经18SrDNA测序鉴定为热带假丝酵母.酶活测定结果显示SB18木糖还原酶主要依赖辅因子还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH),其酶活性远大于木糖醇脱氢酶活性.对SB18进行两级法发酵条件研究,确定补充氮源为尿素和酵母提取物,接种量为0.5 g/L,转速转换时间为36 h.在此条件下由250 g/L木糖摇瓶发酵252 h得到207.65 g/L木糖醇,转化率为83.1%,达到理论值的91.8%.本研究表明酵母菌SB18在高浓度木糖醇的工业生产中具有很大的应用潜力. 相似文献
50.
Glutamic acid (H2glu) and its lithium, sodium
and ammonium monosalts were submitted to thermal analysis using thermogravimetry
(TG) and differential thermal analysis (DTA). The main goal of these studies
was to compare the relative thermal stability and to evaluate the effect of
the counter ion in the thermal decomposition pathways. Salts were obtained
by direct neutralization of the purified acid with LiOH, NaOH or NH4OH
and were characterized by elemental analysis (C, H and N) and IR spectroscopy.
Decomposition occurred after conversion to the pyroglutamic acid or the respective
pyroglutamates and ammonium salt loosing NH3 being
converted to H2glu before decomposition. 相似文献