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21.
Halise Inci Gul Mehtap Tugrak Hiroshi Sakagami Parham Taslimi Ilhami Gulcin Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1619-1624
A series of new 4-(3-(4-substitutedphenyl)-3a,4-dihydro-3H-indeno[1,2-c]pyrazol-2-yl) benzenesulfonamides (7–12) was synthesized starting from 2-(4-substitutedbenzylidene)-2,3-dihydro-1H-inden-1-one (1–6) and 4-hydrazinobenzenesulfonamide. The substituted benzaldehydes from which the key intermediate was prepared by introducing 2- or 4-substituents such as fluorine, hydroxy, methoxy, or the 3,4,5-trimethoxy moieties. The compounds were tested for their cytotoxicity, tumor-specificity and potential as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The 3,4,5-trimethoxy and the 4-hydroxy derivatives showed interesting cytotoxic activities, which may be crucial for further anti-tumor activity studies, whereas some of these sulfonamides strongly inhibited both human (h) cytosolic isoforms hCA I and II. 相似文献
22.
Zahra Mojallal-Tabatabaei Parham Foroumadi Mahsa Toolabi Fereshteh Goli Setareh Moghimi Sussan Kaboudanian-Ardestani Alireza Foroumadi 《Bioorganic & medicinal chemistry》2019,27(16):3682-3691
The development of novel leishmanicidal agents that are capable of being replaced by the available therapeutic options has become a priority. In the present study, the synthesis and leishmanicidal activity of a series of 5-(nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives are described. All compounds appeared to be potent anti-leishmanial agents against both promastigote and amastigote forms of Leishmania major (L. major). Amongst the synthesized compounds, 2-([1,4′-bipiperidin]-1′-yl)-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazole (IIa) and 1-(5-(1-methyl-5-nitro-1H-imidazole-2-yl)-1,3,4-thiadiazol-2-yl)-4-(piperidine-1-yl) piperidine (IIc) are the most effective. Infection index was statistically declined in the presence of all compounds. The analysis of redox-related factors revealed that exposure of L. major cells to IIa and IIc led to an increase in reactive oxygen species (ROS). Furthermore, two compounds were able to increase ROS and NO levels in infected macrophages in a dose-independent manner. In addition, we showed that these compounds induced cell death in promastigotes. Altogether, our results indicated the anti-leishmanial potential of IIa and IIc is mediated by apoptosis through an imbalance in the redox system resulting in the elevation of ROS. This new class of compound seems to hold great promise for the development of new and useful anti-leishmanial agents. 相似文献
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Ting Xiang Neik Kaveh Ghanbarnia Bndicte Ollivier Armin Scheben Anita SevernEllis Nicholas J. Larkan Parham Haddadi Dilantha W. G. Fernando Thierry Rouxel Jacqueline Batley Hossein M. Borhan MarieHlne Balesdent 《Molecular Plant Pathology》2022,23(5):733
Brassica napus (oilseed rape, canola) seedling resistance to Leptosphaeria maculans, the causal agent of blackleg (stem canker) disease, follows a gene‐for‐gene relationship. The avirulence genes AvrLmS and AvrLep2 were described to be perceived by the resistance genes RlmS and LepR2, respectively, present in B. napus ‘Surpass 400’. Here we report cloning of AvrLmS and AvrLep2 using two independent methods. AvrLmS was cloned using combined in vitro crossing between avirulent and virulent isolates with sequencing of DNA bulks from avirulent or virulent progeny (bulked segregant sequencing). AvrLep2 was cloned using a biparental cross of avirulent and virulent L. maculans isolates and a classical map‐based cloning approach. Taking these two approaches independently, we found that AvrLmS and AvrLep2 are the same gene. Complementation of virulent isolates with this gene confirmed its role in inducing resistance on Surpass 400, Topas‐LepR2, and an RlmS‐line. The gene, renamed AvrLmS‐Lep2, encodes a small cysteine‐rich protein of unknown function with an N‐terminal secretory signal peptide, which is a common feature of the majority of effectors from extracellular fungal plant pathogens. The AvrLmS‐Lep2/LepR2 interaction phenotype was found to vary from a typical hypersensitive response through intermediate resistance sometimes towards susceptibility, depending on the inoculation conditions. AvrLmS‐Lep2 was nevertheless sufficient to significantly slow the systemic growth of the pathogen and reduce the stem lesion size on plant genotypes with LepR2, indicating the potential efficiency of this resistance to control the disease in the field. 相似文献
27.
Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism 总被引:19,自引:0,他引:19
Gardiner CM Guethlein LA Shilling HG Pando M Carr WH Rajalingam R Vilches C Parham P 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(5):2992-3001
KIR3DL1 and KIR3DL2 are NK cell receptors for polymorphic HLA-B and -A determinants. The proportion of NK cells that bind anti-KIR3DL1-specific Ab DX9 and their level of binding vary between individuals. To determine whether these differences are due to KIR polymorphism, we assessed KIR3D gene diversity in unrelated individuals and families. Both KIR3DL1 and KIR3DL2 are highly polymorphic genes, with KIR3DS1 segregating like an allele of KIR3DL1. A KIR haplotype lacking KIR3DL1 and KIR3DS1 was defined. The two KIR3DL1 alleles of a heterozygous donor were expressed by different, but overlapping, subsets of NK cell clones. Sequence variation in KIR3DL1 and KIR3DL2 appear distinct; recombination is more evident in KIR3DL1, and point mutation is more evident in KIR3DL2. The KIR3DL1 genotype correlates well with levels of DX9 binding by NK cells, but not with the frequency of DX9-binding cells. Different KIR3DL1 alleles determine high, low, and no binding of DX9 Ab. Consequently, heterozygotes for high and low binding KIR3DL1 alleles have distinct subpopulations of NK cells that bind DX9 at high and low levels, giving characteristic bimodal distributions in flow cytometry. The Z27 Ab gave binding patterns similar to those of DX9. Four KIR3DL1 alleles producing high DX9 binding phenotypes were distinguished from four alleles producing low or no binding phenotypes by substitution at one or more of four positions in the encoded protein: 182 and 283 in the extracellular Ig-like domains, 320 in the transmembrane region, and 373 in the cytoplasmic tail. 相似文献
28.
Residue 3 of β2-microglobulin affects binding of class I MHC molecules by the W6/32 antibody 总被引:4,自引:0,他引:4
Previous studies of class I MHC molecules have shown that the owl monkey (Aotus) possesses at least two variants of the β2-microglobulin (β2m) protein. These two variants have different isoelectric points, and exhibit differential reactivity with the monoclonal
antibody W6/32. We report cDNA sequences of the B2m gene, from W6/32-positive and W6/32-negative Aotus cell lines. The two β2m variants we identified exhibit a single amino acid difference at position three. An arginine residue at position 3 was correlated
with W6/32 reactivity, whereas histidine was associated with non-reactivity. W6/32 reactivity was conferred to a W6/32-negative
Aotus cell line when it was transfected with the B2m from the W6/32-positive cell line. Residue 3 of β2m is located at the surface of the class I molecule. It is also close to position 121 of the MHC class I heavy chain, which
has previously been shown to influence W6/32 antibody binding. We conclude that W6/32 binds a compact epitope on the class
I molecule that includes both residue 3 of β2m and residue 121 of the heavy chain. We examined the distribution of the two β2m motifs in a sample Aotus population using an allele-specific polymerase chain reaction assay. The pattern of β2m segregation we observed matches that which was defined previously by serology. Additionally, we identified laboratory-born
hybrid animals who possess both variants of β2m.
Received: 1 April 1998 / Received: 3 July 1998 相似文献
29.
Parham NJ Srinivasan U Desvaux M Foxman B Marrs CF Henderson IR 《FEMS microbiology letters》2004,230(1):73-83
Escherichia coli is the major aetiological agent of urinary tract infections (UTI). Like diarrhoeagenic strains of E. coli, uropathogenic isolates possess virulence determinants that distinguish them from commensal strains and allow them to produce the clinical manifestations associated with UTI. Several autotransporter proteins have been associated with the ability of E. coli, and other Gram-negative bacteria, to cause disease. Recently, we described the existence within uropathogenic E. coli (UPEC) strains of Sat, a toxin of the serine protease autotransporter of Enterobacteriaceae (SPATE) subfamily. Using features common to proteins secreted via the autotransporter pathway we have identified nine additional autotransporter proteins from the genomic sequence data of UPEC CFT073. Surprisingly, two additional members of the SPATE subfamily were identified. One protein, designated PicU, was homologous to the Pic protein identified in Shigella flexneri and enteroaggregative E. coli. The PicU protein was expressed and investigated for functional activity. 相似文献
30.
Lieberman D Tooby J Cosmides L 《Proceedings. Biological sciences / The Royal Society》2003,270(1517):819-826
Kin-recognition systems have been hypothesized to exist in humans, and adaptively to regulate altruism and incest avoidance among close genetic kin. This latter function allows the architecture of the kin recognition system to be mapped by quantitatively matching individual variation in opposition to incest to individual variation in developmental parameters, such as family structure and co-residence patterns. Methodological difficulties that appear when subjects are asked to disclose incestuous inclinations can be circumvented by measuring their opposition to incest in third parties, i.e. morality. This method allows a direct test of Westermarck's original hypothesis that childhood co-residence with an opposite-sex individual predicts the strength of moral sentiments regarding third-party sibling incest. Results support Westermarck's hypothesis and the model of kin recognition that it implies. Co-residence duration objectively predicts genetic relatedness, making it a reliable cue to kinship. Co-residence duration predicts the strength of opposition to incest, even after controlling for relatedness and even when co-residing individuals are genetically unrelated. This undercuts kin-recognition models requiring matching to self (through, for example, major histocompatibility complex or phenotypic markers). Subjects' beliefs about relatedness had no effect after controlling for co-residence, indicating that systems regulating kin-relevant behaviours are non-conscious, and calibrated by co-residence, not belief. 相似文献