G. Cantelli Forti

RM and log P values of 5-nitroimidazoles

Abstract The chromatographic RM values of a series of nitroimidazoles and their log P values were determined in view of a study of their structure-activity relationships as mutagenic agents. The equations describing the relationship between RM and log P values show a low correlation coefficient. The introduction of the molar refractivity of the R1 and R2 groups yields a significant improvement in the correlation coefficient. The molar refractivity could be an expression of the adsorption activity of the silica gel layer.

Drinking water quality: An in vitro approach for the assessment of cytotoxic and genotoxic load in water sampled along distribution system

An in vitro approach was performed to assess the quality of drinking water collected at two treatment/distribution networks located near the source (Plant #1) and the mouth of River Po (Plant #2). The water was sampled at different points of each distribution network, before (raw water) and after the chlorine dioxide disinfection, and in two points of the pipeline system to evaluate the influence of the distribution system on the amount and quality of the disinfection by-product. Cytotoxicity and genotoxicity of water extracts were evaluated in human peripheral lymphocytes and Hep-G2 cells by the use of the micronucleus (MN) test and Comet assay. Raw water samples of both plants induced cytotoxic effects, but not the increases of MN frequency in Hep-G2 cells and in human lymphocytes. Increases of DNA damage in human leukocytes was detected by Comet assay for raw water of Plant #2 at concentration > or = 0.25 Leq/mL. The disinfection process generally has reduced the toxicity of water samples, even if potential direct DNA-damaging compounds have been detectable in drinking water samples. The proposal approach, if currently used together with chemical analysis, can contribute to improve the monitoring drinking water.

Relationship between the chromatographic behaviour of dermorphin-related oligopeptides and the composition of the mobile phase in reersed-phase thin-layer chromatography: comparison of extrapolated RF values

Abstract The RT>F values of a series of dermorphin-related oligopeptides were determinded in two reversed-phase thin-layer chromatographic systems, the mobile phase being an aqueous buffer alone or mixed with various amounts of methanol or acetone. The linear relationship between the chromatographic behaviour and the composition of the mobile phase yielded very similar extrapolated RF values at 0% of organic solvent in both systems. This shows that the extrapolated RF values are independent of the nature of the organic solvent. In other words, the extrapolated RF values should be related to the partitioning of the compounds between water and silicone oil in a standard system where all the compounds can be compared.

Study of the lipophilic character of a series of β-carbolines

Abstract The lipophilic character of a series of β-carbolines has been studied. The RM values were measured by means of a reversed-phase thin-layer chromatographic (TLC) technique and compared with the RM values obtained by high-performance TLC (HPTLC), the log k′ obtained by high-performance liquid chromatography (HPLC), and the log P values. The best equation shows a very good linear relationship between our RM values and the classical log P values obtained using an octanol—water system. The choice of a pH of 13.0 for the TLC system allowed the measurements of the RM values of molecules in their non-ionized form. The deviations from the linear relationship shown by the RM(HPTLC) and log k′ values of two compounds were due to the fact that both compounds were at least partially ionized at the pH of 7.0 at which the HPTLC and HPLC determinations were carried out.

Quantitative relationship between structure and mutagenic activity in a series of 5-nitroimidazoles

The mutagenic activity of 20 5-nitroimidazoles was tested in Salmonella typhimurium TA-100 strain by means of the Ames test. A multiple regression analysis using the interaction term MR2 X Hb and the chromatographic Rm values yielded the equation: (formula see text); where C is the molar concentration (1 M X 10(-6) of each drug increasing the revertants by five times in the Ames test. The interaction term MR2 X Hb takes into account the positive effect exerted by substituents characterized by higher molar refractivity (MR2) and capable of hydrogen bonding (Hb). It was found that when the electroreduction potentials (EIc.p.) were included, the correlation was not improved.

RM values of xanthone derivatives in structure-activity studies

Abstract The RM values of a series of xanthone derivaties obtained in a chromatographic system were correlated with the calculated log P values. The relationship between lipophilic character and acute toxicity in mice was also studied. The equations describing the structure-activity relationship indicate the importance of lipophilic character in determining the acute toxicity of xanthone derivatives in mice.

Rm Values, retention times and π values of a series of potentially mutagenic nitroimidazo[2,1-b]thiazoles

Abstract The R m values and retention times of a series of nitroimidazo[2,1- b ]thiazoles were obtained by means of thin-layer and high-performance liquid chromatography, respectively. Extrapolated R m and log k′ values were correlated in a statistically significant way with π values calculated according to the literature.

Determination of Lipophilic Character of a Series of Dermorphin-Related Oligopeptioes by Means of Reversed-Phase HPLC

Abstract In recent times there has been a growing interest in the determination of chromatographic parameters of lipophilicity with regard to their use in the study of quantitative structure-activity relationship (1, 2). Very good correlations had been shown between the chromatographic parameters and the log P or π values as a measure of the partition coefficient between octanol and water (2). The reversed phase TLC Rm values in two different chromatographic systems and the reversed-phase HPLC log k′ values of a series of dermorphin-related oligopeptides have been previously determined (3, 4). The purpose of the present work was to study the relationship between log k′ values on one hand and Rm or Σπ values on the other one in view of QSAR studies. In fact the discovery of enkephalin and endorphins with high affinities for opioid receptors added new dimensions to the study of structure-activity relationship of opioid agonists (5, 6, 7, 8).

Photomutagenic Properties of Terfenadine as Revealed by a Stepwise Photostability, Phototoxicity and Photomutagenicity Testing Approach¶

Administration of the second‐generation antihistamine, terfenadine, is sometimes associated with photosensitivity and other skin reactions. To obtain information on its photoreactivity, we used a stepwise experimental approach involving tests for photostability, phototoxicity (PT) (mouse fibroblast cell line [3T3] neutral red uptake [NRU] test) and photomutagenicity (with standard Ames salmonella tester strains TA98, TA100 and TA102). Terfenadine was not phototoxic to cultured mammalian cells under the conditions used (i.e. 5000/161 mJ cm−2 UVA–UVB). Natural sunlight and UV radiations caused considerable drug decomposition and formation of several photoproducts. Addition of the irradiated terfenadine solution (i.e. a mixture of photoproducts) to the tester did not significantly increase background mutation frequency. Irradiation of terfenadine coplated with the TA102 strain induced a clear‐cut photomutagenic response, the magnitude of which was dependent upon the precursor compound concentration and the UV dose (212/7 to 339/11 mJ cm−2 UVA–UVB). These findings demonstrate that in vitro terfenadine is photomutagenic in absence of PT. Further in vitro and in vivo studies are therefore needed to provide an adequate safety assessment of the photochemical genotoxicity–carcinogenicity potential of terfenadine. In the meantime, patients should be advised to avoid excessive exposure to sunlight.

Methadone affects the histochemical pattern of xenobiotic-metabolizing enzymes in the liver of pregnant rats.

Enzyme histochemistry performed on the liver of pregnant and non pregnant rats indicates that methadone (ME) does not cause direct damage to the cells. On the other hand, the enzyme aldehyde dehydrogenase was decreased in the periportal tract of the liver lobule of pregnant rats treated with 10 mg/kg ME for 20 days. NADPH dehydrogenase was increased in the central areas of the liver lobule within 3 days of ME treatment. It is suggested that a derangement of xenobiotic metabolizing enzymes in the liver, as well as in other organs, may be contribute to some of the alterations observed in ME treated animals.