Microsomal Oxidation of Hydroxyl Radical Scavenging Agents
Robert A. Greenwald in CRC Handbook of Methods for Oxygen Radical Research, 2018
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.
The Thymus in the Regulation and Control of Cell Growth
Nate F. Cardarelli in The Thymus in Health and Senescence, 2019
In 1963 promine was separated into two fractions, one promoting growth and the second inducing sterility.32 The latter, called “infertine”, was found only in the thymus. It was also noted in the same report that the older the animal, the more promine and less retine found. Infertine was not a protein, though it probably contained nitrogen.33 The molecular weight is low and it is soluble in carbon tetrachloride, water, and methanol.34 The sterilizing action of infertine is reversible in sexually mature Swiss albino mice, but effects are irreversible if administered at an appropriate dose to prepubertal animals.34 Szent-Gyorgyi et al. comment that promine “makes old animals behave like young ones”.35 In the discussion section of the cited report, Sandstrom suggests that (1) young animals produce steroids in the thymus, and (2) a thymic hormone maintains activity by those genes responsible for youth. It is suggested that cell division is regulated by a balance between promine and retine.36 Retine has both ketone and aldehyde groups present and is a methylglyoxal derivative. Further studies by Eglud indicated that retine was not only present in the calf thymus, but also in clams, mushrooms, and human urine!37 Infrared spectra indicated the presence of a carbonyl group, an aldehyde, unsaturation, and a hydroxy group. It is probably an open chain ketonic compound, and since the UV absorption peaks shift with pH, ketoenol complex tautomerization is suggested.37 Glyoxyl derivatives, such as the semicarbazones are known cancerostats.38 Interestingly, ketoaldehydes are found in all tissue examined, except tumors.
Biochemical Methods of Studying Hepatotoxicity
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
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.
Thio- and selenosemicarbazones as antiprotozoal agents against Trypanosoma cruzi and Trichomonas vaginalis
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Alexandra Ibáñez-Escribano, Cristina Fonseca-Berzal, Mónica Martínez-Montiel, Manuel Álvarez-Márquez, María Gómez-Núñez, Manuel Lacueva-Arnedo, Teresa Espinosa-Buitrago, Tania Martín-Pérez, José Antonio Escario, Penélope Merino-Montiel, Sara Montiel-Smith, Alicia Gómez-Barrio, Óscar López, José G. Fernández-Bolaños
In the present work we have accomplished the preparation of an ample number of thio(seleno)semicarbazones as potential antiparasitic agents against T. cruzi (responsible for Chagas disease) and T. vaginalis (responsible for trichomoniasis) with a mode of action different to that of classical nitroheterocyclic compounds, the current only available drugs for treating both parasitic infections. We have carried out an extensive analysis of SARs upon modification of the stereoelectronic effects of the aromatic substituents, together with the nature of the chalcogen atom (S vs. Se). Thiosemicarbazide 31, bearing a naphthyl residue on N-4, exhibited the best trypanocidal activity at the epimastigote stage of two different parasitic strains, with similar profile to that of the reference drug benznidazole.
Leishmanicidal candidate LASSBio-1736, a cysteine protease inhibitor with favorable pharmacokinetics: low clearance and good distribution
Published in Xenobiotica, 2018
Barbra Sanches Moraes, Francine Johansson Azeredo, Jessica Cristina Izoton, Marina Amaral, Eliezer de Jesus Barreiro, Rodrigo José Freddo, Teresa Dalla Costa, Lídia Moreira Lima, Sandra Elisa Haas
In the last years, the therapeutic arsenal for the treatment of VL has been extremely limited, and although conventional therapies continue to play a major role, high toxicity, severe adverse effects, development of resistance, ineffectiveness in curing the disease and high cost indicate the need to develop new drugs. Considering the arguments raised, several drug candidates against this disease have been studied. Among possible targets, cysteine protease inhibitors have drawn attention due to their activity against species of Trypanosoma (Alves et al., 2015; Du et al., 2002; Raghav et al., 2010; Steverding et al., 2012) and Leishmania (Alves et al., 2015; Schroder et al., 2013). Alves et al. (2015) developed semicarbazone derivatives of LASSBio-1022 that showed trypanosomicidal and leishmanicidal activities, particularly LASSBio-1483. The same research group synthesized, by molecular hybridization between the fragments of arylhydrazide of LASSBio-1111 and acylhydrazone of LASSBio-1064 (salicylaldehyde 4-chloro benzoylhydrazone), a new series with the same leishmanicidal molecular target (cysteine proteases) (Moreira Lima et al., 2014). Among these compounds, the drug candidate LASSBio-1736 is particularly interesting (Figure 1).
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.
Related Knowledge Centers
- Acetone
- Amine
- Antiviral Drug
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- Ketone
- Organic Chemistry
- Aldehyde
- Semicarbazide
- Nitrofurazone
- Thiosemicarbazone