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Biomedical subjects

C Benezra

Publications and source records attributed to C Benezra.

70 records · Page 4Linked to original sources
PubMed1978

Synthesis of and allergic contact dermatitis to bicyclo-[2,2,1]-heptyl-alpha-methylene-gamma-butyrolactones derived from norbornene and camphene.

Three new lactones, 2-oxo-3-methylene-4,7-methanobenzofuran and two alpha-methylene spirolactones, 3',3'-dimethylspiro(2-oxo-3-methylenefuran-5,2'-norbornane), were synthesized and their skin activity was tested on one human volunteer and on guinea pigs. The man, sensitized to Frullania, was found sensitive to the above lactones and also reacted to frullanolide and alantolactone. The guinea pigs, experimentally sensitized to alantolactone, cross-reacted to 2-oxo-3-methylene-4,7-methanobenzofuran and the two alpha-methylene spirolactones, and also to isolantolactone and frullanolide.

4-Butyrolactone↗
PubMed1975

Contact allergy to Frullania and Laurus Nobilis: cross-sensitization and chemical structure of the allergens.

Cross-sensitization between two plant allergens, Frullania and Laurus Nobilis (L.), has been demonstrated in Strabourg. A review of the haptens isolated from Frullania outlines the importance of the purification of allergen to ascertain the nature of the causative agent. New results on laurel oil point to the possibility of a common denominator (the a-methylene gamga-butyrolactone moiety) between this plant and Frullania; former results are re-interpreted and analyzed. In conclusion, the importance of physico-chemical methods used to purify and isolate haptens, and help in their definition, is stressed.

4-Butyrolactone↗
PubMedDate not supplied

Bihaptens with 5- and 6-methyl-substituted alkylcatechols and methylene lactone functional groups: tools for hapten (allergen or tolerogen)-protein interaction studies.

In order to investigate hapten-protein interactions in vivo, potential skin sensitizers 1-3, with two different haptenic ends, (a) a catechol, a 5-methylcatechol, and a 6-methylcatechol respectively, and (b) an alpha-methylene-gamma-butyrolactone moiety, separated by a straight 10-carbon chain, have been prepared and used to sensitize guinea pigs. Related "monohapten lactones" 19-21, containing an electrophilic alpha-methylene-gamma-butyrolactone moiety connected to the protected catechol structures, and "monohapten catechols" 25-27, containing a reduced alpha-methyl-gamma-butyrolactone linked to the catechol, also have been prepared. Bihaptens 1 and 2 which were found to have very close biological activities appear to react with proteins through the catechol ring, indicating a low importance of the C-6 position in the binding of catechols with amino acids. In contrast, bihapten 3 was found to react through both the catechol and lactone ring. The influence of amino and thiol binding sites on the biological activity (allergy or tolerance) as well as the influence of the sensitizing method are discussed.

Allergens↗
PubMedDate not supplied

Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 1. Synthesis and electrophilic reactivity studies of alpha-(omega-substituted-alkyl)-gamma,gamma-dimethyl-gamma-butyrolacton es and correlation of skin sensitization potential and cross-sensitization patterns with structure.

A series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 1), a series of alpha-(2-X-substituted-ethyl)-gamma,gamma-dimethyl-gamma-butyrolactones (series 2), where X is a leaving group, and the compound alpha-(3-bromopropyl)-gamma,gamma-butyrolactone (3) were synthesized. Their reactions as electrophiles toward n-butylamine, used as a model for nucleophilic groups on skin proteins whose in vivo chemical modification leads to skin sensitization, were investigated. The compounds of series 1 were shown to react via a two-stage elimination--Michael addition sequence whereby the elements of HX are eliminated to form alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone, which reacts more slowly with n-butylamine to give alpha-[(N-butylamino)methyl]-gamma,gamma-dimethyl-gamma-butyrolactone. The compounds of series 2 and compound 3 were shown to react with n-butylamine via a single-stage substitution reaction to give respectively alpha-[2-(N-butylamino)ethyl]- and alpha-[3-(N-butylamino)propyl]-gamma,gamma-dimethyl-gamma-butyrolactones . Rate constants for these reactions have been determined, and it is found that substitution reactions of series 2 and compound 3 are slower than Michael addition of alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone, which in turn is slower than the elimination reactions of series 1. The results of guinea pig skin sensitization tests on these compounds were found to be consistent with the above findings in that the compounds of series 1 were found to be in general much stronger sensitizers than those of series 2 and compound 3. The results of cross-challenge tests indicate that sensitizing compounds from series 2 were cross-reactive with both series 1 and compound 3 but that compound 3 is only weakly cross-reactive with series 1. These observations indicated that for these compounds a difference of two carbon atoms between the determinant groups transferred to protein had a markedly greater effect than a difference of one carbon atom on antigenic specificity.

4-Butyrolactone↗
PubMedDate not supplied

Structure-activity relationships for contact allergenic potential of gamma,gamma-dimethyl-gamma-butyrolactone derivatives. 2. Quantitative structure-skin sensitization relationships for alpha-substituted-alpha-methyl-gamma,gamma-dimethyl-gamma-butyrolactone s.

A skin sensitization cross-challenge dataset for a series of alpha-(X-substituted-methyl)-gamma,gamma-dimethyl-gamma-butyrolactones is analyzed in terms of the relative alkylation index (RAI) model. The data analyzed consist of guinea pig sensitization response data for tests in which one lactone derivative is used for the induction stage and then the animals are challenged with another lactone derivative to elicit the response. RAI values are based on calculated log P (octanol/water) values together with measured relative rate constants for reactions of the lactones with n-butylamine to form alpha-methylene-gamma,gamma-dimethyl-gamma-butyrolactone. Plots of biological response against RAI for induction (RAIi) for sets of data in which the same compound is used for challenge have the double-sigmoid shape typical of sensitization response--RAIi plots, with some points in the overload region. Relative elicitation potential (REP) values, defined in terms of the biological response when sensitized animals are challenged with the compound in question relative to the response when the same animals are challenged with a chosen reference compound, are obtained. Consistent with the RAI model, plots of REP against RAIc, the RAI value corresponding to challenge, are linear and the slopes of plots corresponding to different reference compounds are, within the limits of experimental error, in the same ratio as the REP values of the reference compounds. Finally, multiple linear regression analysis gives a quantitative structure-activity relationship (QSAR) covering the complete set of cross-challenge data, relating the biological responses to the RAIi and RAIc values.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMedDate not supplied

Molecular aspects of allergic contact dermatitis to plants. Recent progress in phytodermatochemistry.

A classification of plants based on the chemical structures of their skin sensitizers is presented. A whole range of chemical structures of contact sensitizers exists in plants containing sesquiterpene lactones (Compositae, Frullania, Lauraceae etc.), tulipalin (Tulipa, Alstroemeria etc.), quinones (Primula and tropical woods), long chain phenols (Anacardiaceae, Ginkgoaceae) and miscellaneous structures such as aldehydes, ketones, terpene hydrocarbons etc. Knowledge of allergens in various plants allows prediction of cross-reactivity.

Allergens↗