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201.
Zhao ZY San M Duprey JL Arrand JR Vyle JS Tucker JH 《Bioorganic & medicinal chemistry letters》2012,22(1):129-132
Single nucleotide polymorphisms within a sequence of a gene associated with prostate cancer were identified using oligodeoxynucleotide probe sequences bearing internal anthracene fluorophores proximal to the SNP site. Depending upon the nature of the synthesised target sequences, probe-target duplex formation could lead to enhanced or attenuated fluorescence emission from the anthracene, enabling detection of a proximal base-pair as either matching or mismatching. 相似文献
202.
Olmo ED Diaz-González R Escarcena R Carvalho L Bustos LA Navarro M Feliciano AS 《Bioorganic & medicinal chemistry letters》2012,22(1):440-443
Twenty compounds selected as representative members of three series of long-chain 1,2-diamines, 2-amino-1-alkanols and 1-amino-2-alkanols structurally related to dihydrosphingosin, were synthesized and tested in vitro for their ability to inhibit the sleeping sickness parasites Trypanosoma bruceirhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC(50) values in the submicromolar range, with selectivity indexes up to 39 related to the respective cytotoxicity values for Vero cells. The parasite phenotype detected after treatment with the most potent compounds showed irreversible cell morphology alterations of the flagellar pocket that lead to inhibition of cell growth and parasite death. 相似文献
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Dong-Mei Zhang Yong Li Wai San Cheang Chi Wai Lau Shun-Ming Lin Qian-Lan Zhang Nan Yao Ying Wang Xin Wu Yu Huang Wen-Cai Ye 《PloS one》2012,7(10)
Cajaninstilbene acid (CSA) is a major active component present in the leaves of Cajanus cajan (L.) Millsp. The present study explores the underlying cellular mechanisms for CSA-induced relaxation in rat renal arteries. Vascular reactivity was examined in arterial rings that were suspended in a Multi Myograph System and the expression of signaling proteins was assessed by Western blotting method. CSA (0.1–10 µM) produced relaxations in rings pre-contracted by phenylephrine, serotonin, 9, 11-dideoxy-9α, 11α-epoxymethanoprostaglandin F2α (U46619), and 60 mM KCl. CSA-induced relaxations did not show difference between genders and were unaffected by endothelium denudation, nor by treatment with NG-nitro-L-arginine methyl ester, indomethacin, ICI-182780, tetraethylammonium ion, BaCl2, glibenclamide, 4-aminopyridine or propranolol. CSA reduced contraction induced by CaCl2 (0.01–5 mM) in Ca2+-free 60 mM KCl solution and by 30 nM (−)-Bay K8644 in 15 mM KCl solution. CSA inhibited 60 mM KCl-induced Ca2+ influx in smooth muscle of renal arteries. In addition, CSA inhibited contraction evoked by phorbol 12-myristate 13-acetate (PMA, protein kinase C agonist) in Ca2+-free Krebs solution. Moreover, CSA reduced the U46619- and PMA-induced phosphorylation of myosin light chain (MLC) at Ser19 and myosin phosphatase target subunit 1 (MYPT1) at Thr853 which was associated with vasoconstriction. CSA also lowered the phosphorylation of protein kinase C (PKCδ) at Thr505. In summary, the present results suggest that CSA relaxes renal arteries in vitro via multiple cellular mechanisms involving partial inhibition of calcium entry via nifedipine-sensitive calcium channels, protein kinase C and Rho kinase. 相似文献
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Maliogka VI Salvador B Carbonell A Sáenz P León DS Oliveros JC Delgadillo MO García JA Simón-Mateo C 《Molecular Plant Pathology》2012,13(8):877-886
Subisolates segregated from an M-type Plum pox virus (PPV) isolate, PPV-PS, differ widely in pathogenicity despite their high degree of sequence similarity. A single amino acid substitution, K109E, in the helper component proteinase (HCPro) protein of PPV caused a significant enhancement of symptom severity in herbaceous hosts, and notably modified virus infectivity in peach seedlings. The presence of this substitution in certain subisolates that induced mild symptoms in herbaceous hosts and did not infect peach seedlings suggested the existence of uncharacterized attenuating factors in these subisolates. In this study, we show that two amino acid changes in the P1 protein are specifically associated with the mild pathogenicity exhibited by some PS subisolates. Site-directed mutagenesis studies demonstrated that both substitutions, W29R and V139E, but especially W29R, resulted in lower levels of virus accumulation and symptom severity in a woody host, Prunus persica. Furthermore, when W29R and V139E mutations were expressed concomitantly, PPV infectivity was completely abolished in this host. In contrast, the V139E substitution, but not W29R, was found to be responsible for symptom attenuation in herbaceous hosts. Deep sequencing analysis demonstrated that the W29R and V139E heterogeneities already existed in the original PPV-PS isolate before its segregation in different subisolates by local lesion cloning. These results highlight the potential complexity of potyviral populations and the relevance of the P1 protein of potyviruses in pathogenesis and viral adaptation to the host. 相似文献
209.
Perez-Meseguer J Del Olmo E Alanis-Garza B Escarcena R Garza-González E Salazar-Aranda R Feliciano AS de Torres NW 《Bioorganic & medicinal chemistry》2012,20(13):4155-4163
Twenty-five derivatives of the natural diterpene leubethanol, including several potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity against the H37Rv strain of Mycobacterium tuberculosis. Several compounds showed antimycobacterial potencies similar to that of the lead compound and two of them displayed higher selectivity indexes. 相似文献
210.
C1027 is a potent antitumor agent that damages DNA. It has the unusual ability to produce double strand breaks and interstrand cross-links (ICLs) intracellularly, which enable it to initiate concurrent ataxia-telangiestasia mutated (ATM) and Rad-3 related (ATR) independent damage responses. The latter form of damage is not well characterized. We have examined the effect of DNA sequence on C1027 reactivity and found it to be more diverse than previously thought. In addition, analysis of the chemical stability of ICLs suggests that they result from reaction with the deoxyribose ring on one strand but direct addition to a nucleobase on the opposite strand. 相似文献