Unfused heterobicycles as amplifiers of phleomycin. VII. Some triazolyl-, thiadiazolyl- and oxadiazolyl-pyridines and related pyrimidines

1983 ◽  
Vol 36 (7) ◽  
pp. 1469 ◽  
Author(s):  
DJ Brown ◽  
WB Cowden

Syntheses are described for several 4-(1',2',4'-triazol-3'yl)pyridines, 3-and 4-(1',3',4'-thiadiazol-2'-yl)-pyridines, 3- and 4-(1',3',4'-oxadiazol-2'-yl)pyridines, 5-(1',3',4'-thiadiazol-2'-yl)pyrimidines and 5-(1',3',4'-oxadiazol-2'-yl)pyrimidines, all provided with a β-dimethylaminoethylthio side chain at the 5-position of the five-membered ring. The activities of these compounds as amplifiers of phleomycin-G against an in vitro culture of Escherichia coli B are tabulated and discussed.

1981 ◽  
Vol 34 (11) ◽  
pp. 2423 ◽  
Author(s):  
DJ Brown ◽  
BB Buttler ◽  
WB Cowden ◽  
GW Grigg ◽  
D Kavulak ◽  
...  

Syntheses are described for 4-(thiazol-4'-yl)pyridines, each 2'-substituted by a dialkylaminoalkyl, dialkylaminoalkylthio or dialkylaminoalkylamino side chain; for 2- and 3-(thiazol-4'-yl)pyridines with a 2'-dimethylaminoethylthio substituent; for 4-(thiazol-2'-yl)pyridines with either a 4'- or a 5'-dialkylaminoalkylcarbamoyl substituent; and for some analogous compounds. The above and similarly substituted 2,4'-, 4,5'- and 5,5'-bipyrimidines have been screened for activity as amplifiers of phleomycin-G against Escherichia coli B by an improved in vitro procedure. The results are tabulated and discussed.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Du ◽  
R Li ◽  
Q Zhang ◽  
W Wang

Abstract Study question what is the source, prevalence, and influence of microbial contamination on in vitro fertilization (IVF) and embryo transfer (ET) cycles? Summary answer Microbial contamination mainly occurs on Day 2, most caused by Escherichia coli carried with semen. ICSI could prevent contamination effectively and get good clinical outcomes. What is known already Microbial contamination occurs in IVF-ET system occasionally, which is hard to stop happening. The IVF culture system and laboratory environment, the patients’ follicular fluid and semen are not absolutely sterile, while the antibiotics in culture medium isn’t effective for all microbe types, and the artificial operations may bring in microbes. Generally, microbial contamination leads to degradation of embryos, reduction the number of embryos available, and infection of female reproductive tract, which would increase the cost of patients’ time, money, and bring psychological damages. A better understanding of embryo contamination in IVF culture system is of added value. Study design, size, duration A total of 29583 IVF-ET cycles were enrolled in this prospective observational study, from January 2010 to December 2020, included 70 microbial contamination cycles discovered in Day1-Day3 (D1-D3) of in vitro culture. Follicular fluid and semen saved on oocyte retrieval day, and culture medium contaminated were examined and identified for microorganisms at each contamination cycle. Participants/materials, setting, methods Compared the contamination rate of different insemination methods (IVF/ICSI/IVF+ICSI), different in vitro culture days (D1-D3), and different samples examination (follicular fluid, semen, culture medium) respectively, identified the source of microorganism types, compared the IVF culture outcomes and clinical outcomes between total contamination group (TC group, 42 cases) and partial contamination group (PC group, 28 cases). Main results and the role of chance A total of 70 microbial contamination cases occurred in 29583 oocyte retrieving cycles (0.24%), and it was observed only in IVF embryos but never in ICSI (Intracytoplasmic sperm injection) embryos. 38 contamination cases occurred on D2 with a highest ratio (54.3%) compared to D1 (32.9%) and D3(12.9%); Compared with follicular fluid, semen was the main cause inducing contamination from D1 to D3, and Escherichia coli in semen and culture medium, Enterococcus faecalis in follicular fluid proved to be the most common sources. Compared with TC group, the PC group showed a lower rate of No-available embryos (21.4% vs 81.0%) and a higher rate of blastocyst formation (41.2% vs 28.6%), In addition, the clinical pregnancy rate of PC group was higher than that of TC group in both fresh and frozen-thawed embryo transfer cycles (31.3% vs 16.7%, 38.5% vs 0.0%). Limitations, reasons for caution Further study is still necessary to better understand the sources that induce microbial contamination embryos, and more efficient methods are required to remove the microbes on these contaminated embryos so as better develop and manage a sterile micro-environment for successful embryo growth. Wider implications of the findings: The differential embryonic microbe types associated to different IVF culture and clinical outcomes in patients undergoing IVF-ET might have profound implications for understanding the microbial sources and making a better management of IVF culture system. Trial registration number Not applicable


1974 ◽  
Vol 19 (5) ◽  
pp. 321-328 ◽  
Author(s):  
Harold Werbin ◽  
Bala D. Lakchaura ◽  
John Jagger

2014 ◽  
Vol 14 (1) ◽  
pp. 77 ◽  
Author(s):  
Egil AJ Fischer ◽  
Cindy M Dierikx ◽  
Alieda van Essen-Zandbergen ◽  
Herman JW van Roermund ◽  
Dik J Mevius ◽  
...  

1988 ◽  
Vol 157 (1) ◽  
pp. 47-53 ◽  
Author(s):  
K. S. Kim ◽  
J. H. Kang ◽  
A. S. Cross ◽  
B. Kaufman ◽  
W. Zollinger ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0179853 ◽  
Author(s):  
Alexey Fomenkov ◽  
Zhiyi Sun ◽  
Deborah K. Dila ◽  
Brian P. Anton ◽  
Richard J. Roberts ◽  
...  

2007 ◽  
Vol 79 (12) ◽  
pp. 2179-2188 ◽  
Author(s):  
A. Ian Scott ◽  
Charles A. Roessner

The genetic engineering of Escherichia coli for the over-expression of enzymes of the aerobic and anaerobic pathways to cobalamin has resulted in the in vivo and in vitro biosynthesis of new intermediates and other products that were isolated and characterized using a combination of bioorganic chemistry and high-resolution NMR. Analyses of these products were used to deduct the functions of the enzymes that catalyze their synthesis. CobZ, another enzyme for the synthesis of precorrin-3B of the aerobic pathway, has recently been described, as has been BluB, the enzyme responsible for the oxygen-dependent biosynthesis of dimethylbenzimidazole. In the anaerobic pathway, functions have recently been experimentally confirmed for or assigned to the CbiMNOQ cobalt transport complex, CbiA (a,c side chain amidation), CbiD (C-1 methylation), CbiF (C-11 methylation), CbiG (lactone opening, deacylation), CbiP (b,d,e,g side chain amidation), and CbiT (C-15 methylation, C-12 side chain decarboxylation). The dephosphorylation of adenosylcobalamin-phosphate, catalyzed by CobC, has been proposed as the final step in the biosynthesis of adenosylcobalamin.


1969 ◽  
Vol 24 (7) ◽  
pp. 903-910 ◽  
Author(s):  
R. Süssmuth ◽  
F. Lingens

1. The stability of NNMG with respect to pH was investigated. A maximum, with a half-life of 40 hours, was found in phosphate-citric acid buffer at pH 5. The stability decreases quickly with increasing concentration of hydroxyl ions. At the optimal mutation rate (pH 6, 37°, and shaking) the half-live is only 14,4 hours.2. NNMG uptake (using labelled NNMG) and mutation rate in the range pH 3,5 — 8,0 show an optimum at pH 6,0/6,5 for both Escherichia coli B and the red ad- mutant E 188 of Saccharomyces cerevisiae. The pH-dependence of NNMG uptake and mutation rate is similar.3. The methylation of nucleic acids by means of [3H]-methyl-NNMG or [14C] -methyl-NNMG in phosphate-citric acid at 37° while shaking increases with the growing concentration of hydroxyl ions. At the optimal mutation rate, however, NNMG methylates relatively poor.4. Incorporation of radioactive NNMG into Escherichia coli B results in labelling of nucleic acids and proteins. The labelling of DNA shows an optimum at pH 6. The extent of methylation was found to be higher in vivo than in vitro.5. In the presence of cysteine or β-mercaptoethanol nucleic acids are methylated more intensively than in the cysteine-free control experiment. After one hour the methylation was about twentyfold higher in the presence of cysteine or β-mercaptoethanol compared to the cysteine-free control experiment. The methylation in presence of SH-compounds shows a maximum at pH 6. The explanation of both a higher methylation rate and its optimum at pH 6 suggests the activation of methylation by means of sulphhydryl-groups.


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