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61.
62.
Synthesis and investigation of the conversion reactions of pyrimidine‐thiones with nucleophilic reagent and evaluation of their acetylcholinesterase,carbonic anhydrase inhibition,and antioxidant activities 下载免费PDF全文
Parham Taslimi Afsun Sujayev Fikret Turkan Emin Garibov Zübeyir Huyut Vagif Farzaliyev Sevgi Mamedova İlhami Gulçin 《Journal of biochemical and molecular toxicology》2018,32(2)
The conversion reactions of pyrimidine‐thiones with nucleophilic reagent were studied during this scientific research. For this purpose, new compounds were synthesized by the interaction between 1,2‐epoxy propane, 1,2‐epoxy butane, and 4‐chlor‐1‐butanol and pyrimidine‐thiones. These pyrimidine‐thiones derivatives ( A–K ) showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) isoforms I and II. AChE inhibition was in the range of 93.1 ± 33.7–467.5 ± 126.9 nM. The hCA I and II were effectively inhibited by these compounds, with Ki values in the range of 4.3 ± 1.1–9.1 ± 2.7 nM for hCA I and 4.2 ± 1.1–14.1 ± 4.4 nM for hCA II. On the other hand, acetazolamide clinically used as CA inhibitor showed Ki value of 13.9 ± 5.1 nM against hCA I and 18.1 ± 8.5 nM against hCA II. The antioxidant activity of the pyrimidine‐thiones derivatives ( A–K ) was investigated by using different in vitro antioxidant assays, including Cu2+ and Fe3+ reducing, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH?) radical scavenging, and Fe2+ chelating activities. 相似文献
63.
Synthesis of some novel pyridine compounds containing bis‐1,2,4‐triazole/thiosemicarbazide moiety and investigation of their antioxidant properties,carbonic anhydrase,and acetylcholinesterase enzymes inhibition profiles 下载免费PDF全文
Nilufer Bulut Umit M. Kocyigit Ibrahim H. Gecibesler Taner Dastan Huseyin Karci Parham Taslimi Sevgi Durna Dastan Ilhami Gulcin Ahmet Cetin 《Journal of biochemical and molecular toxicology》2018,32(1)
Some novel derivatives of thiosemicarbazide and 1,2,4‐triazole‐3‐thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine‐2,5‐dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine‐2,5‐dicarboxylate ( 1 ). The reaction of dimethyl‐2,5‐pyridinedicarboxylate ( 1 ) with hydrazine hydrate good yielded pyridine‐2,5‐dicarbohydrazide ( 2 ). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3–8 h afforded 1,4‐disubstituted thiosemicarbazides ( 3a–e ). Base‐catalyzed intra‐molecular dehydrative cyclization of these intermediates furnished the 4,5‐disubstituted bis‐mercaptotriazoles ( 4a–e ) in good yield (85%–95%). Among the target compounds, 2,2′‐(pyridine‐2,5‐diyldicarbonyl)bis[N‐(p‐methoxyphenyl)hydrazinecarbothioamide] ( 3c ) showed very high activity with value of 72.93% against 1,1‐diphenyl‐2‐picrylhydrazyl free radical at the concentration of 25 μg/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with Kis in the range of 3.07 ± 0.76–87.26 ± 29.25 nM against AChE, in the range of 1.47 ± 0.37–10.06 ± 2.96 nM against hCA I, and in the range of 3.55 ± 0.57–7.66 ± 2.06 nM against hCA II, respectively. 相似文献
64.
Synthesis and discovery of potent carbonic anhydrase,acetylcholinesterase, butyrylcholinesterase,and α‐glycosidase enzymes inhibitors: The novel N,N′‐bis‐cyanomethylamine and alkoxymethylamine derivatives 下载免费PDF全文
Parham Taslimi Cuneyt Caglayan Vagif Farzaliyev Oruj Nabiyev Afsun Sujayev Fikret Turkan Ruya Kaya İlhami Gulçin 《Journal of biochemical and molecular toxicology》2018,32(4)
During this investigation, N,N′‐bis‐azidomethylamines, N,N′‐bis‐cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N‐bis‐cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the α‐glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with Ki values in the range of 0.15–13.31 nM for α‐glycosidase, 2.77–15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12–21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33–73.23 nM for AChE, and 3.84–48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances. 相似文献
65.
Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis,characterization, acetylcholinesterase,butyrylcholinesterase, and carbonic anhydrase inhibitory properties 下载免费PDF全文
Parham Taslimi Sabiya Osmanova Cuneyt Caglayan Fikret Turkan Sabira Sardarova Vagif Farzaliyev Afsun Sujayev Nastaran Sadeghian İlhami Gulçin 《Journal of biochemical and molecular toxicology》2018,32(9)
The thiolation reaction was carried out in a benzene solution at 80°C and p‐substituted ketones and mercaptoacetic acid in a molar ratio (1:4) of in the presence of a catalytic amount of toluene sulfonic acids. The enzyme inhibition activities of the novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives were investigated. These novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives showed good inhibitory action against acetylcholinesterase (AChE) butyrylcholinesterase (BChE), and human carbonic anhydrase I and II isoforms (hCA I and II). AChE inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. Many clinically established drugs are carbonic anhydrase inhibitors, and it is highly anticipated that many more will eventually find their way into the market. The novel synthesized compounds inhibited AChE and BChE with Ki values in the range of 0.64–1.47 nM and 9.11–48.12 nM, respectively. On the other hand, hCA I and II were effectively inhibited by these compounds, with Ki values between 63.27–132.34 and of 29.63–127.31 nM, respectively. 相似文献
66.
R. S. Wells Mark T. Seielstad Mike Bunce Dolly B. Tyan Endashaw Bekele Peter Parham 《Immunogenetics》1997,46(3):173-180
The complete sequence of a new HLA-C allele, Cw
*
1701, was determined from a South African Zulu individual. Unique features that distinguish Cw
*
1701 from other HLA-C alleles include multiple point substitutions and an 18 nucleotide insertion in exon 5, which encodes the transmembrane domain.
In a phylogenetic analysis of HLA-C sequences, Cw
*
1701 forms a third, distinct allelic lineage. A comparison of the transmembrane domain of Cw
*
1701 with other HLA-B and -C alleles reveals that duplications and deletions have been common in the evolution of these loci. A polymerase chain reaction
based typing method was used to determine the distribution of this unusual allele in human populations. In contrast to the
other two lineages of HLA-C alleles, the Cw
*
17 lineage is found at high frequencies only in populations of African descent. In addition, the HLA-B/Cw
*
17 haplotype diversity is higher in Africa.
Received: 29 June 1996 / Revised: 20 December 1996 相似文献
67.
Dilan Ozmen Ozgun Cem Yamali Parham Taslimi Ilhami Gulcin 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1498-1501
The effects of isatin Mannich bases incorporating (1-[piperidin-1-yl (P1)/morpholin-4-yl (P2)/N-methylpiperazin-1-yl (P3)]methyl)-1H-indole-2,3-dione) moieties against human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoenzymes hCA I and hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes were evaluated. P1–P3 demonstrated impressive inhibition profiles against AChE and BChE and also inhibited both CAs at nanomolar level. These inhibitory effects were more powerful in all cases than the reference compounds used for all these enzymes. This study suggests that isatin Mannich bases P1–P3 are good candidate compounds especially for the development of new cholinesterase inhibitors since they were 2.2–5.9 times better inhibitors than clinically used drug Tacrine. 相似文献
68.
Purification of papain-solubilized histocompatibility antigens from a cultured human lymphoblastoid line, RPMI 4265. 总被引:1,自引:0,他引:1
M J Turner P Cresswell P Parham J L Strominger D L Mann A R Sanderson 《The Journal of biological chemistry》1975,250(12):4512-4519
HL-A antigens having specificities HL-A2, HL-A7, HL-A12 have been solubilized by papain treatment of membrane preparations from the cultured human lymphoblastoid cell line RPMI 4265 and purified about 80-fold by chromatography on carboxymethylcellulose, Sephadex G-150, and diethylaminoethylcellulose columns. Separation of HL-A2 from a mixture of HL-A7 and HL-A12 was achieved on the final DEAE-cellulose column. The yield was about 1 mg of protein of each antigen preparation per 100 g of packed, frozen cells. On sodium dodecyl sulfate gel electrophoresis both preparations showed two polypeptide bands. The smaller subunit of 12,000 daltons is common to all HL-A preparations and has been shown to be identical with beta2-microglobulin. The larger subunit is a glycopeptide and in the HL-A7, 12 preparation was resolved into a duplex of 34,000 and 37,000 daltons. The HL-A2 preparation showed a single band at 34,000 daltons. On isoelectric focusing under nondenaturing conditions, the preparation showed multiple bands, all of which contained both subunits and retained antigenic activity. On isoelectric focusing in the presence of 6 M urea a single band for beta2-microglobulin and multiple bands for the larger subunit were seen. This charge heterogeneity of the larger subunit has been shown to be due to variable amounts of sialic acid. When HL-A antigen preparations were subjected to Sephadex G-100 chromatography in the presence of 3 M KCl, no separation of the two subunits was observed. 相似文献
69.
The monoclonal antibody M1340.2 defines a novel subtype of HLA-1340 that is expressed by the Sweig cell line. This molecule, called HLA-B40*, lacks an antigenic determinant that is common to HLA-137 and the HLA-Bw60 subtype of HLA-1340. Genes encoding HLA-B40* and HLA-BW60 have now been isolated and the amino acid sequences of these proteins compared with other HLA-13 locus molecules. These results show that HLA-B40* is a unique protein which differs from HLA-BW60 by eight amino acid substitutions. Comparison of the sequences for HLA-B40*, -Bw60, and -B7 localizes the MB40.2 epitope to a cluster of three substitutions at positions 177, 178, and 180 at the end of the 2 domain. Gene conversion or reciprocal recombination are postulated to have transferred this cluster of substitutions, and their associated epitope, during the evolution of HLA-B locus genes. The epitope may consist of an a helical segment which is exclusively found on MB40.2-positive molecules. 相似文献
70.
P Parham 《Journal of immunology (Baltimore, Md. : 1950)》1983,131(6):2895-2902
Methods for the production and purification of F(ab')2 fragments from BALB/c monoclonal IgG1, IgG2a, and IgG2b with pepsin and other proteases were examined. The overall susceptibility to degradation is IgG2b greater than IgG2a greater than IgG1. Stable F(ab')2 can be produced in good yield from IgG1 with pepsin at pH 3.5 to 4.0 and can be made directly by pepsin treatment of ascites fluids or cell culture supernatants containing IgG1. IgG2a is cleaved in two steps by pepsin, first to F(ab')2 and then to Fab'. With carefully chosen conditions, F(ab')2 can be obtained in acceptable yield. The primary cleavage for the IgG2a heavy chain appears to be on the COOH terminal side of the interheavy chain disulfides, and secondary cleavage is on the NH2-terminal side. For IgG2b the reverse is true, and F(ab')2 has not been obtained in useful amounts; however, the primary cleavage of IgG2b appears to be assymetric with respect to the two heavy chains, and Fab/c fragments that have one Fab plus Fc can be made. Digestion with elastase resulted in the best yield of Fab/c. This finding may provide a method for retaining cytotoxicity in monoclonal antibodies against cell surface antigens while eliminating their capacity to modulate. The cleavage patterns of the three classes of IgG are rationalized in terms of the structure of their hinge regions. 相似文献