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Biochemical Methods of Studying Hepatotoxicity
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Prasada Rao S. Kodavanti, Harihara M. Mehendale
For the determination of formaldehyde, the procedure described here is that of Nash (1953). The Nash reaction has been widely used, since it is simple, fast, and accurate. Formaldehyde formed during incubation will be trapped as the semicarbazone and measured by colorimetric procedure, based on Hantzsch reaction (Nash, 1953; Cochin and Axelrod, 1959). The Hantzsch reaction requires a β-diketone (acetylacetone), an aldehyde (formaldehyde), and an amine (NH3 from ammonium acetate). The resulting product is 3,5-diacetyl-1,4-dihydrolutidine, which can be measured at A415.
The Renewal of Interest in Nitroaromatic Drugs
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Nicolas Primas, Caroline Ducros, Patrice Vanelle, Pierre Verhaeghe
However, the replacement of the 5-nitrofuran moiety by a 5-nitrothiophen led to a significant decrease in activity (Paula et al. 2009). Related (5-nitro-2-furyl)propene derivatives were also prepared and exhibited in vivo activity against T. cruzi. The semicarbazone (31) (Figure 9) was the most potent in the histopathological studies of Chagasic animals, where it showed greater efficacy in the presence of amastigotes and inflammatory infiltrates in heart and muscle than reference drug nifurtimox (8) (Cabrera et al. 2009).
Microsomal Oxidation of Hydroxyl Radical Scavenging Agents
Published in Robert A. Greenwald, CRC Handbook of Methods for Oxygen Radical Research, 2018
Arthur I. Cederbaum, Gerald Cohen
Two different procedures can be used to assay for the oxidation of the alcohols: gas chromatography, and trapping of the aldehyde or acetone as the semicarbazone derivative. Both procedures are identical to those described for t-butanol. For the analysis of head space by gas chromatography experiment, the following retention times (minutes) have been obtained: acetaldehyde, 0.40; l-butyraldehyde, 0.80; acetone, 0.65; ethanol, 1.1; l-butanol, 3.7; isopropanol, 2.5. Relative peak areas are quantitated by using standard curves prepared by adding known amounts of aldehyde or acetone to “zero-time” controls. For the semicarbazone detection experiment, flasks with center wells containing semicarbazide are used, and after an overnight diffusion period, the absorbance of the acetaldehyde-, butyraldehyde-, or acetone-semicarbazones are determined at 224 nm.
Recent developments on triazole nucleus in anticonvulsant compounds: a review
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Yogeeswari’ team always devotes to the research of various aryl-substituted semicarbazones as potential anticonvulsant agents. Based on the heat of triazole moiety in the study of anticonvulsants, they launched a program to cyclise these aryl semicarbazones, which would lead to 1,2,4-triazoles. A new series of 4,5-diphenyl-2H-1,2,4-triazol-3(4H)-one (45, Figure 8) were synthesised, and four animal seizures models [maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and subcutaneous picrotoxin (scPIC)] were conducted to evaluate their anticonvulsant activities. The effect of cyclisation of semicarbazones template depended on the substituents. Some more potent derivatives with 2,4/2,5-dimethylphenyl groups were obtained, but the activity was decreased or maintained for the 2,6-dimethyl/4-fluorophenyl derivatives. compound 45a (Figure 8) had increased the GABA level more than 10 times compared to the control in rat brain at 100 mg/kg, which indicated that the cyclised aryl semicarbazones (4,5-diphenyl-2H-1,2,4-triazol-3(4H)-ones) exhibited anticonvulsant activity via GABA-mediation76.
A patent update on therapeutic applications of urease inhibitors (2012–2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Abdul Hameed, Mariya Al-Rashida, Maliha Uroos, Syeda Uroos Qazi, Sadia Naz, Marium Ishtiaq, Khalid Mohammed Khan
Our research group has recently reported in vitro urease inhibition by semicarbazone derivatives (134 [43], 148 [44], 19/20 [45]). N-substituted hydroxylurea and its derivatives have also been reported as urease inhibitors. Among the derivatives of hydroxyurea, m-methyl and m-methoxy-phenyl substituted hydroxyurea were found to be the most potent urease inhibitors. The N-substituted hydroxylurea derivatives were more potent inhibitors as compared to the unsubstituted hydroxyurea [46].
Novel approaches to the discovery of selective human monoamine oxidase-B inhibitors: is there room for improvement?
Published in Expert Opinion on Drug Discovery, 2019
Paolo Guglielmi, Simone Carradori, Alessandra Ammazzalorso, Daniela Secci
Semicarbazones, thiosemicarbazones, and hydrazones have been proposed as promising scaffolds with a large plethora of pharmacological actions including MAO inhibitory property as new MTDLs aimed to be effective against NDDs. Within the last five years, 77 new compounds were synthesized and tested as MAO inhibitors keeping constant the common CONHN = linker and varying the two opposite tails: the former comprehended benzodioxol-5-yl, 5-methoxybenzothiazol-2-yl, 6-nitrobenzothiazol-2-yl and 5-nitrothiazol-2-yl rings, whereas the hydrazonic nitrogen was functionalized with mono- or disubstituted aryl groups or isatin-based compounds (Figure 16). The choice of these substituents involved the analysis of size, more or less rigid, more or less electron-rich heteroaryl rings leading to final compounds with varying degree of hydrophobicity to derive robust structure–activity relationships. These compounds were assessed for in vitro MAO and AChE inhibition, kinetic and reversibility studies, antioxidant activity (DPPH), neurotoxicity (rotarod apparatus and NIH/3T3 mouse embryonic fibroblast cell line), ADME parameters and BBB permeability in silico and molecular modelling studies to further identify the binding site, orientation and interactions of inhibitors within respective enzyme active sites and determine the free energies of binding and inhibition constants of the experimentally tested compounds. SAR studies were described in Figure 16. Collectively, they were good inhibitors of human and rat MAO-B, endowed with a reversible mechanism of action and ancillary properties useful for the CNS penetration and activity as MTDLs. They possessed dual action in the micromolar range against AChE and were classified as non-toxic compounds. From the analysis of molecular modelling data, it is generally assumed that the heterocycle was located toward the FAD in the substrate cavity, engaging productive interactions with Tyr435 (aromatic cage), whereas the hydrazonic portion spanned toward the entrance cavity, thus leading to a complete occupation of both areas as reported for safinamide [74–77].