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861.
《Bioorganic & medicinal chemistry letters》2020,30(2):126819
Twenty-nine nucleoside analogues have been synthesized and evaluated in a cell based assay for their ability to activate the human Stimulator of Interferon Genes (hSTING), a key protein of the innate immune defense. Some 6-O-alkyl nucleoside analogues activate hSTING without associated cytotoxicity. SAR and combination studies were performed to decipher possible activation mechanism. The described nucleoside hSTING activators represent first-in-class modulators of the innate immune defense; a highly relevant target for antiviral, antibacterial, anticancer or Alzheimer’s disease treatments and may present advantages over other types of hSTING activators. 相似文献
862.
Atish Barua Pritha Choudhury Joy Krishna Maity Sukhendu Bikash Mandal Suvra Mandal 《Free radical research》2019,53(1):57-67
Therapeutic efficacy of nucleoside analogues (NAs) like Gemcitabine, 5-fluorouracil in cancer treatment is already well established. Most of the known NAs are highly toxic to normal cells due to its non-specific action; thus searching for non-toxic NAs are still going on. For that purpose we have synthesised nine different NAs by alteration of their structural and functional groups. The aim of present study is to investigate the therapeutic potential of NAs against mice bearing breast adenocarcinoma cells at IC50 dose for 10 days treatment schedule. Results of the present study showed that, among the seven nucleoside analogues, NA-7 and NA-9 showed maximum therapeutic efficacy in controlling cancer cells by inhibiting cell proliferation and inducing apoptosis without any adverse effects to normal host cells. Additionally, NAs significantly decreased the tumour burden and enhanced survivability of host through generation of reactive oxygen species in tumour cells. These ultimately led to DNA damage, depolarisation of mitochondrial membrane potential and apoptosis in tumour cells. To find out the molecular mechanisms, we showed that administration of NA-7 and NA-9, down- regulating the expression of Bcl-2, cyclin D1, C-myc, P-21 and up-regulating the expression of P-53, Cyt-c, Bax, caspase-3 and caspase-9. The results suggest that NA-7 and NA-9 exhibits significant antitumor activity than 5-fluorouracil by modulating the cell cycle checkpoints and inducing apoptosis in Ehrlich ascites carcinoma (EAC)-bearing mice. Additionally, NA-7 and NA-9 did not show any clastogenic effect on bone marrow cells at sub-lethal dose. Thus, the present study clearly suggested therapeutic benefit of NAs by augmenting anticancer efficacy and diminishing toxicity to the host. 相似文献
863.
Broadbridge Robert J. Sharma Ram P. 《International journal of peptide research and therapeutics》1999,6(5-6):335-341
Summary Phosphorylation reactions are key meditors in a variety of biochemical signal processes. Research into the selective inhibition
of protein tyrosine kinases to generate anticancer agents has madeO-phosphotyrosyl analogues important pharmacological tools. The simple procedures reported here involving the formation of
interative peptide libraries together with the development of a selective and sensitive bead-binding assay have made it possible
to rapidly screen peptides incorporatingO-phosphotyrosyl surrogates (includingO-phospho-2,3,5,6-tetrafluorotyrosine, 4-(phosphono)hydroxymethyl-phenylalanine and 4-(phosphono)fluoromethyl-phenylalanine)
for their potential to inhibit the protein tyrosine kinase p56lck. These procedures can be easily adapted to combinatorical peptide libraries. 相似文献
864.
Ma Wenli Mosberg Henry I. 《International journal of peptide research and therapeutics》1999,6(2-3):179-183
Summary A straightforward approach for the synthesis of several new, aryl-substituted derivatives of the conformationally constrained
phenylalanine analogue 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) is described. Tic, nitrosubstituted at the 6
or 7 position, was prepared by base-catalyzed cyclization of diethyl acetamidomalonate with α,α-dibromo-4-nitro-o-xylene followed by decarboxylation and deacylation under refluxing conditions in aqueous HCl. Catalytic hydrogenation of
nitro-Tic in the presence of 10% Pd/C afforded amino-Tic, which was then converted to iodo-Tic by a modified Sandmeyer reaction.
Both amino-Tic and iodo-Tic can easily be transformed to other substituents. 相似文献
865.
Marco António Teixeira Zullo Ladislav Kohout Mariangela de Burgos Martins de Azevedo 《Plant Growth Regulation》2003,39(1):1-11
In this paper the definitions of brassinolide, brassinolide activity andbrassins are reviewed, and definitions for the terms brassin, naturalbrassinosteroids and brassinosteroid analogues, based on biosynthetic reasoningand structure similarity are proposed. 相似文献
866.
867.
G. L. Mendz Andrew J. Shepley Stuart L. Hazell Mark A. Smith 《Archives of microbiology》1997,168(6):448-456
The requirements for purine nucleotide synthesis, the effects of purine analogues, and the metabolism of adenine in the bacterium
Helicobacter pylori were investigated employing cell culture techniques and one-dimensional NMR spectroscopy. Bacterial cells grew and proliferated
in media lacking preformed purines, indicating that H. pylori can synthesize purine nucleotides de novo to meet its requirements. Blocking of this pathway in the absence of sufficient
preformed purines for salvage nucleotide synthesis led to cell death. Analogues of purine nucleobases and nucleosides taken
up by the cells were cytotoxic, suggesting that salvage routes could be exploited for therapy. Adenine or hypoxanthine were
able to substitute for catalase in supporting cell growth and proliferation, suggesting a role for these bases in maintaining
the microaerophilic conditions essentially required by the bacterium.
Received: 23 May 1997 / Accepted: 17 July 1997 相似文献
868.
NBS类植物抗病基因保守结构域的克隆为利用简并引物扩增抗病基因同源序列提供了可能.根据抗病基因Gro1-4、Gpa2、N等的P-loop和GLPL保守结构域设计简并引物,分离甘薯近缘野生种三浅裂野牵牛NBS类型抗病基因同源序列,共获得6条相关序列,核苷酸序列的相似性为48%~97%,推测氨基酸序列的相似性在25.2%~95.1%之间.系统进化分析表明,6条三浅裂野牵牛RGA序列可分为2个不同的类群:TIR-NBS和non-TIR-NBS.三浅裂野牵牛RGA序列与源自甘薯的RGA序列有很高的相似性,这在一定程度上反映了三浅裂野牵牛与甘薯之间的亲缘关系.分离的6条RGA序列分别命名为ItRGA1~ItRGA6,GenBank登录号分别为DQ849027~DQ849032. 相似文献
869.
CHRISTER LÖFSTEDT BILL S. HANSSON HENDRIK J. DIJKERMAN WIM M. HERREBOUT 《Physiological Entomology》1990,15(1):47-54
ABSTRACT In field-trapping experiments the unsaturated analogues ( E )-6-, ( E )-12-, and ( Z )-12-tetradecenyl acetate were as attractive to male Yponomeuta rorellus Latr. as the native pheromone component tetradecyl acetate. All four analogues attracted more males than virgin females did, whereas ( Z )-6-, ( E )-11-, ( Z )-10- and ( Z )-11-tetradecenyl acetate were essentially non-attractive. Addition of 1–30% of ( Z )-11-tetradecenyl acetate to the pheromone tetradecyl acetate reduced the attraction to less than 2%. Flight tunnel experiments with Y. rorellus confirmed the activity of the ( E )-6- and ( E )-12-tetradecenyl acetates and demonstrated the activity of ( E )-7-tetradecenyl acetate as well. These analogues elicited orientation behaviour, upwind flight and landing at the odour source as frequently as the native pheromone did. Single sensillum recordings from male Y. rorellus showed two types of cells in most sensilla. A large spike amplitude cell was stimulated by tetradecyl acetate and the unsaturated analogues ( E )-11-, ( E )-6- and ( E )-12-tetradecenyl acetate, and to a lower extent by the ( Z )-6-, ( Z )-11- and ( Z )-12-isomers. A cell with medium spike amplitude was stimulated by ( Z )-9-tetradecenyl and ( Z )-11-hexadecenyl acetate. Some sensilla contained a third cell firing with a small spike amplitude which was activated by ( Z )-11-tetradecenol. Thus the tetradecyl acetate receptor was stimulated not only by the behaviourally active analogues, but also by behavioural antagonists. The interaction of ( E )-11-tetra-decenyl acetate and tetradecyl acetate with the same antennal receptor cell was also demonstrated in Y.cagnagellus . Electrophysiological discrimination between behavioural attractants and antagonists and the role of behavioural antagonists in the interspecific relations between Y.rorellus and sympatric closely related species are discussed. 相似文献