Biomedical subjects

W P Van Bennekom

Publications and source records attributed to W P Van Bennekom.

8 recordsLinked to original sources

PubMed1995

3,5-Disubstituted analogues of paracetamol. Synthesis, analgesic activity and cytotoxicity.

Seven 3,5-disubstituted analogues of paracetamol were synthesised in order to compare their physicochemical, pharmacological and toxicological properties with those of paracetamol (4'-hydroxyacetanilide, acetaminophen). Oxidation of the phenolic structure is likely involved in the analgesic action of paracetamol as well as in its toxification by cytochrome P450. The effect of disubstitution adjacent to the phenolic hydroxyl group was studied in order to establish possible structure-activity relationships. 3,5-Substituents with electron-donating capacities (R = -CH3, -OCH3, -SCH3) decreased the half-wave oxidation potential substantially by 0.07 V to 0.16 V, whereas electron-withdrawing substituents (R = -F, -Cl, -Br, or -I) increased the oxidation potential by 0.04 V to 0.06 V when compared to paracetamol. Electron-donating substituents (R = -CH3, -OCH3, -SCH3) increased the mouse brain cyclooxygenase inhibiting capacity of paracetamol. Electron-withdrawing halogen substituents (R = -F, -Cl, -Br or -I) decreased this inhibiting capacity. In agreement with this, the in vivo analgesic activity of the 3,5-dihalogenated analogues was lower when compared to paracetamol. Electron-donating substituents (R = -CH3, -OCH3, -SCH3) decreased the cytotoxicity of paracetamol, when measured as leakage of lactate dehydrogenase from freshly isolated rat hepatocytes, almost completely. Most 3,5-dihalogen substituents (R = -F, -Cl or -Br) diminished it slightly. The fourth electron-withdrawing substituent (R = -I) strongly lowered the cytotoxicity of paracetamol in this test system. In conclusion, a higher cycylooxygenase inhibitory potency of 3,5-disubstituted analogues of paracetamol seemed to correlate with a lower cytotoxicity. 3,5-Disubstituted analogues with electron-donating substituents might therefore be safer analgesics than paracetamol itself. The opposite probably applies to analogues of paracetamol with electron-withdrawing substituents at the 3- and 5- positions of the aromatic nucleus.

Acetaminophen↗

PubMed1992

On-line phase-transfer catalysed dansylation of phenolic compounds followed by normal-phase liquid chromatography with fluorescence detection.

A study of the on-line phase-transfer catalysed dansylation of phenolic compounds is presented. The extraction-dansylation is performed in the extraction coil of a home-made flow-injection extraction unit. After phase separation, the organic phase is fed to a normal-phase liquid chromatographic system with fluorescence detection. Ethynyloestradiol, oestradiol and paracetamol are used as test compounds. The influence of temperature on the reaction is examined. Calibration graphs showed good linearity (r greater than 0.996) and limits of detection are satisfactory (8 x 10(-7) M for ethynyloestradiol, 2 x 10(-6) M for oestradiol and 5 x 10(-7) M for paracetamol). The method is not applicable for the assay of oxychinoline, phenylephrine and morphine.

Acetaminophen↗

PubMed1988

A study of the metal complexation behaviour of some penicillins, cephalosporins and their derivatives.

The metal complexation behaviour of several beta-lactam antibiotics and derivatives is explained, based on the results of potentiometric titrations. The (organo)metal ions used were (organic derivatives of) transition elements and elements with a filled d-subshell. The emphatic class b (organo)metal ions Ag(I), Hg(II) and C6H5Hg(I) form the most stable complexes with the studied ligands: Hg(II) is the most suited ion. The alkaline degradation products and hydroxamic acid derivatives of penicillins and cephalosporins are very similar to penicillamine in their complexation behaviour. This emphasizes the dominant role of the thiol group as site of complexation. A scheme for stepwise complex formation with Hg(II) and Ag(I) is presented. The availability of the thiol group is used to explain small differences in complexation behaviour between penicillin derivatives on the one hand, and cephalosporin derivatives and penicillamine on the other.

Cephalosporins↗

PubMed1987

Polarographic determination of extraction constants.

The extraction constant of three organic compounds containing nitrogen as a picrate ion pair in a water-chloroform system were determined by following polarographically the picrate concentration in the aqueous phase as a function of the added amount of reagent. The extraction constants were also determined spectrophotometrically (via batch extraction). The obtained results are in good agreement. The proposed method is applicable for extraction constants with values between 10(3) and 10(9).

Ions↗

PubMed1987

Penicillins and cephalosporins. Physicochemical properties and analysis in pharmaceutical and biological matrices.

Penicillins and cephalosporins belong to the most prescribed antibiotics. Despite the relatively extended knowledge of these drugs, the qualitative and quantitative analysis of the compounds still gives rise to many problems. These difficulties are due to the chemical instability of the common beta-lactam nucleus, the minor differences in chemical structures between the analogues, and the complex and relatively fast degradation of the compounds in aqueous solutions. In this review a compilation of the physicochemical properties, the degradation routes and methods for analysis of these substances in biological and other matrices is presented.

Animals↗

PubMed1985

Generalized theory for two-phase ion-pair and complexometric titrations. I. Two-phase titrations without side reactions.

A systematic theoretical treatment of the two-phase titration based on ion-pair and metal-complex formation is presented. Equations for the titration curve, accuracy, equivalence point and choice of the indicator are derived. Much attention is paid to the parameters determining the 'titratability' viz. extraction constant, distribution constant, phase volume ratio and the concentration of the analyte. Special attention is given to the role of intermediate ion-pair and metal-complex formation in the aqueous phase. The ion-pair formation in aqueous solution is examined closer by means of the relationship between the association constant in water, the degree of dissociation of the ion pair (alpha) and the concentration of the counter ion. The merits of this theoretical treatment are illustrated with literature examples.

Chemical Phenomena↗

PubMed1985

Generalized theory for two-phase ion-pair and complexometric titrations. II. Two-phase titrations with side reactions.

For the two-phase titration based on ion-pair and metal-complex formation full attention is given to side reactions in both phases. Their significance for the applicability of this type of titration is evaluated. Side reactions in the aqueous phase diminish and in the organic phase promote the 'titratability'. Equations for the calculation of the side reaction coefficients, the titration curve and the selection of the optimal pH and minimal side reaction interference (in the aqueous phase) are presented. Finally a full description is given of the two-phase titration including all parameters determining the 'titratability'. The merits of the developed theory are illustrated by literature examples.

Chemical Phenomena↗

PubMed1984

Nitroprusside, antihypertensive drug and analytical reagent. Review of (photo)stability, pharmacology and analytical properties.

A review of physical, chemical, analytical and pharmacological properties of nitroprusside is presented. In view of the pharmaceutical applications of nitroprusside special attention is given to the discussion of the (photo)degradation, the stability of the pharmaceutical formulations, the application as a reagent in pharmaceutical analysis and the redox behaviour.

Animals↗