ChemInform Abstract: SYNTHESE UND LOKALANAESTHETISCHE WIRKUNG VON N-PIPERIDINO-METHYL-4-ALKOXYBENZAMIDEN

Schoenenberger, H.; Bindl, L.; Petter, A.; Zwez, W.

doi:10.1002/chin.197104277

Cited by 3 publications

(5 citation statements)

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“…Cytotoxicity increases by an increase in the deamination ratio. 22) The higher the deamination ratio, the higher the cytotoxicity of the compounds. 22) Two pathways may be suggested for the cytotoxicity of the azines: 1.…”

Section: Discussionmentioning

confidence: 99%

“…22) The higher the deamination ratio, the higher the cytotoxicity of the compounds. 22) Two pathways may be suggested for the cytotoxicity of the azines: 1. Azine compounds (D1-D4), which are bifunctional agents, undergo deamination to give compound 3, which contains biologically active unsaturated groups.…”

Section: Discussionmentioning

confidence: 99%

“…The a,b-unsaturated ketone is an active center for nucleophilic attack. The biological activities of Mannich bases, such as antimicrobial, [1][2][3]21,22) cytotoxic and anticancer 6,9,23) activities, have been attributed to these liberated a,b-unsaturated ketones which can alkylate nucleophiles, especially thiol groups 1,6,24,25) rather than amino and hydroxyl groups, 26) by Michael type addition reactions of nucleophiles to a,b-unsaturated ketones.27) In addition, enzyme-catalyzed alkylation of the thiol group of cystein with a,b-unsaturated carbonyl compounds has been observed. …”

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confidence: 99%

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Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Gül

Vepsäläinen

et al. 2003

Biological & Pharmaceutical Bulletin

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Mannich bases have several biological activities such as antimicrobial, [1][2][3][4][5] cytotoxic, [6][7][8][9] anticancer, 10) analgesic, 11) anti-inflammatory, 12,13) diuretic 14,15) and anticonvulsant [16][17][18][19] activities. An amino ketone, Mannich base, containing at least one activated hydrogen atom at the b position to an amino function, can undergo deamination in vivo 20) or under simulated in vitro conditions 1,3,6) to liberate the corressponding a,b-unsaturated ketones. The a,b-unsaturated ketone is an active center for nucleophilic attack. The biological activities of Mannich bases, such as antimicrobial, [1][2][3]21,22) cytotoxic and anticancer 6,9,23) activities, have been attributed to these liberated a,b-unsaturated ketones which can alkylate nucleophiles, especially thiol groups 1,6,24,25) rather than amino and hydroxyl groups, 26) by Michael type addition reactions of nucleophiles to a,b-unsaturated ketones.27) In addition, enzyme-catalyzed alkylation of the thiol group of cystein with a,b-unsaturated carbonyl compounds has been observed. 28)The antimicrobial activity of a,b-unsaturated ketones is due to their reactions with essential thiol groups in bacteria and fungi, resulting in b-ketothioethers.29) Electron densities on b-carbons are lower 30) than on a-carbons in various unsaturated ketones, and thus the attack of the nucleophils should occur at the b-carbon atoms. It was also shown that increased antimicrobial activity was associated with an increased breakdown of the Mannich bases.29) Similarly, a number of a,b-unsaturated ketones have alkylating ability against biologically important nucleophiles to produce cytotoxicity. 21,23) The amino group in Mannich bases would increase the water solubilizing property of the molecule, which may assist in transportation of the compound to the site of action.Production of thiol adducts in the stability studies, 1,3,6) carried out under in vitro physiological conditions (in phosphate buffer with pH 7.4, at 37°C), with 2-mercaptoethanol, various unsaturated ketones or Mannich bases, suggests that a,bunsaturated ketones and Mannich bases producing unsaturated ketones by deamination to exert their antimicrobial activities by thiol alkylation of unsaturated ketones.Clark and co-workers 31) found that the thiol adduct had the greatest fungitoxicity, which was probably due to the same reaction. Dimmock et al. (1994) have shown that Mannich bases of conjugated styryl ketones inhibit one or more of the following enzymes in the glutathione metabolic pathway: namely, glutathione S-transferases, glutathione reductase, gamma-glutamyl transpeptidase and glutathione peroxidase in Candida albicans. 32) They concluded that the antifungal activity of the Mannich bases of conjugated styryl ketones may be due, at least in part, to interference with the GSH metabolic pathway. In one of our previous studies, we observed that mono-Mannich bases and bis Mannich bases decrease the total glutathione level in a dose-dependent manner when Jurkat cells are exposed to the co...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Gül

Vepsäläinen

et al. 2003

Biological & Pharmaceutical Bulletin

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“…However, derivatization must be performed to eliminate adsorption of these compounds to the chromatographic support. The separation and quantitation of sulfa drugs, alone (16)(17)(18) and in pharmaceutical preparations (19, 20), by high-pressure liquid chromatography (HPLC) were described. Recently, methods were proposed for sulfamethazine residues in bovine tissue (21) and for sulfamethazine, sulfamerazine, sulfathiazole, and their metabolites in cattle urine (22).…”

Section: Accepted Formentioning

confidence: 99%

Synthesis of Diastereoisomeric 4-Dimethylamino-3-phenyl-2-butanols and Related Esters for Antimicrobial Evaluation

Dimmock

Kowal

et al. 1978

Journal of Pharmaceutical Sciences

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“…1,6,19,20) It has been shown that there is a relationship between the increased antimicrobial activity and an increased breakdown of Mannich bases. 21) The development of resistance to current antifungal therapeutics continues to drive the search for more effective new agents. It is reported that Mannich bases such as those of conjugated styryl ketones, 4) and isatin N-Mannich bases 22) have antifungal activity.…”

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confidence: 99%

Antifungal Evaluation of Bis Mannich Bases Derived from Acetophenones and Their Corresponding Piperidinols and Stability Studies

Gül

Ojanen

Hänninen

2002

Biological & Pharmaceutical Bulletin

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The development of resistance to current antifungal therapeutics drives the search for effective new agents. The fact that some acetophenone-derived Mannich bases had shown antifungal activities in our previous studies led us to design and synthesize acetophenone-derived bis Mannich bases, B1-B5, bis(b b-aroylethyl)methylamine hydrochlorides, to evaluate their antifungal activity. These bis Mannich bases were then converted to the corresponding piperidinols, C1-C5, which are structural isomers of bis derivatives, 3-aroyl-4-aryl-1-methyl-4-piperidinol hydrochlorides, to see alterations in biological activity. A stability study of B1 and C1 was also carried out to estimate whether they alkylate the thiols. All compounds studied have shown antifungal activity, especially against dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Microsporum canis), in the concentration range studied (2-128 m mg/ml). The activity was especially apparent against T. tonsurans. All compounds had at least equal antifungal activity compared with the reference compound amphotericin-B against T. tonsurans. Bis Mannich bases were generally found to be more potent compounds than their structural isomer piperidinols. The results of our stability studies suggest that thiol alkylation may contribute to the antifungal activity of the Mannich bases synthesized. Even though all compounds showed antifungal activity against dermatophytes, bis Mannich bases B1, B2, B4, and B5 appear to have potential for developing novel antifungal agents against dermatophytes.

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ChemInform Abstract: SYNTHESE UND LOKALANAESTHETISCHE WIRKUNG VON N-PIPERIDINO-METHYL-4-ALKOXYBENZAMIDEN

Abstract: Erhitzen von Paraformaldehyd, Piperidin und einem Amid führt zu den N‐Piperidinomethyl‐4‐alkoxybenzamiden (I).

Cited by 3 publications

References 1 publication

Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Synthesis of Diastereoisomeric 4-Dimethylamino-3-phenyl-2-butanols and Related Esters for Antimicrobial Evaluation

Antifungal Evaluation of Bis Mannich Bases Derived from Acetophenones and Their Corresponding Piperidinols and Stability Studies

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