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Effect of Solute Structure on Transport of Radiotracers
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
Long-chain 18F fatty acids have been studied by Knust et al. for study of regional metabolism in the heart.21 The 18F-fluoro fatty acids 9-10-[18F] stearic, 2-[18F] hexa-decanoic, and 17-[18F] heptadecanoic showed varied uptake. The 2-[18F] stearic had little uptake in the myocardium but had increased uptake in the liver. On the other hand, the 18F label in the middle or at the end of the carbon chain showed uptake and clearance similar to the 11C-labeled fatty acid palmitic acid in which there is rapid concentration within 1 min and clearance by a slow and a fast component. The 16-[18] hexadecanoic acid and the 17-[18F] heptadecanoic have different turnover pools and different rates. Nearly all the 18F in the heart from 17-[18F] heptadecanoic was recovered as 18F fluoride, while practically no fluoride 18F was found for 16-[18F] hexadecanoic acid. These results were interpreted on the basis of the odd-even rule in which β oxidation of even numbered fatty acids produces [18F] fluoroacetic acid while odd-numbered fatty acids result in β-[18F] fluoroproprionic acid. The latter compound undergoes dehalogenation to produce free fluoride, but the fluoroacetic acid undergoes further metabolism in the citric acid cycle.21
Miscellaneous pesticides*
Published in Bev-Lorraine True, Robert H. Dreisbach, Dreisbach’s HANDBOOK of POISONING, 2001
Bev-Lorraine True, Robert H. Dreisbach
The sodium salt of fluoroacetic acid (CH2FCOONa; 1080) is a water-soluble, synthetic chemical used in the past as a rodenticide. Fluoroacetate is no longer marketed in the USA, but fluoroacetamide is still available.
Halogen Labeled Compounds (F, Br, At, Cl) *
Published in Garimella V. S. Rayudu, Lelio G. Colombetti, Radiotracers for Medical Applications, 2019
More recently, Knust et al.149 synthesized a series of 18F-fatty acids (2-fluorostearic, 16-fluorohexadecanoic, 17-fluoroheptadecanoic, and 9,10-fluorostearic acids) to study the regional metabolism in the heart and liver of mice. 18F-2-Fluorostearic acid showed little uptake in the myocardium, but high accumulation in the liver. This was explained as the inhibition of the formation of coenzyme-A ester due to the presence of p-halogen. Furthermore, enzymatic dehalogenation by glutathione-S-alkyltransferase was not observed for other alkyl chlorides or alkyl fluorides. The other fluorinated fatty acids also showed uptake and elimination behavior in the myocardium similar to 111C-palmitic acid. It was shown that β-oxidation of even-number fatty acids such as 16-fluorohexadecanoic acids resulted in forming fluoroacetic acid, which in turn undergoes further metabolism into the citric acid cycle, whereas the odd-number carbon fatty acids ended up with 18F-β-fluoropropionic acid, which does not enter the metabolic cycle, and undergoes catabolization by dehydrofluorination to form free fluoride. This is reflected by the uptake of fluoride in the bone in the following order: 17-fluorodecanoic acid > 9- or 10-fluorostearic acid > 16-fluorodecanoic acid > 2-fluo-rostearic acid. The fact that the bone activity of the isomeric mixtures of 9- and 10-fluorostearic acids was in between that of 17- and 16-fluorodecanoic acids can be explained that 9-fluorostearic acid is metabolized to β-fluorododecanoic acid, whereas 10-fluorostearic acid is metabolized to 2-fluorodecanoic acid, and further metabolism is blocked, as is the case for 2-fluorostearic acid. Recent reports by Stöcklin et al.151 also showed similar results, i.e., all the three ω-fluorofatty acids (18F-16-fluoropalmitic acid, 18F-17-fluoroheptadecanoic acid, and 18F-9, 10-fluorostearic acid) exhibited comparable myocardial uptake as l-1C-palmitic acid.
Applications of fluorine to the construction of bioisosteric elements for the purposes of novel drug discovery
Published in Expert Opinion on Drug Discovery, 2021
As part of a program to identify compounds with superior potency and a better pharmacokinetic profile as an alternative clinical development candidate to nicotinic acid [178–181], Qin and coworkers have reported on the identification of a thiobarbituric acid (49) derivative identified from a high-throughput screen that showed moderate in vitro potency as a GPR109a agonist [182]. Sequential SAR investigations in order to improve the potency initially focused on the C-2 vector with the goal to identify a suitable replacement for the reactive, sensitive thiol-group in 49 (Figure 8). Most replacements tested led to a complete loss of activity, but the hydroxymethyl derivative (1100 nM, not shown) showed modest levels of activity, which was attenuated through formation of the corresponding ether (3393 nM, not shown). Installation of fluoroalkyl groups at the C-2 position presented an interesting profile with the trifluoromethyl group (50) showing similar activity to the hydroxymethyl variant (not shown), while the difluoro- (51) and monofluoro-methyl (52) analogues showed significant improvements in potency, which were superior even to the initial SH-based lead (49). Switching from the difluoromethyl to a fluorochloromethyl (2705 nM, not shown) led to a > 8-fold loss of potency. Despite being marginally better in terms of activity than the difluoromethyl derivative (51), the monofluoro-compound (52) was deprioritized owing to its potential to produce toxic α-fluoroacetic acid.
Therapeutic potential of polysaccharide extracted from fenugreek seeds against thiamethoxam-induced hepatotoxicity and genotoxicity in Wistar adult rats
Published in Toxicology Mechanisms and Methods, 2019
Amal Feki, Imen Jaballi, Boutheina Cherif, Naourez Ktari, Manel Naifar, Fatma Makni Ayadi, Rim Kallel, Ons Boudawara, Choumous Kallel, Moncef Nasri, Ibtissem Ben Amara
FWEP was hydrolyzed in 250 µl of 2 M tri-fluoroacetic acid (TFA) at 100 °C for 1 h. Excess TFA was removed by evaporation, and the hydrolysate was washed thoroughly with water and lyophilized. The lyophilized powder was dissolved in 100 µl of water, and a 5 µl aliquot was used for thin-layer chromatography (TLC). Migration was performed twice on a silica gel TLC plate (20 × 20 cm) using n-butanol:ethanol:water (2:1:1, v/v). Carbohydrates were visualized by heating the TLC plate after spraying with 5% (v/v) sulfuric acid in ethanol. Arabinose, xylose, fructose, glutamic acid, gluconic acid, glucose, galactose, mannose, and rhamnose were used as standard monosaccharaides.