A structure activity relationship study of geranial derivatives

• Background: Fragrances are common causes of contact allergy. Skin exposure to geranial is frequent since citral (mixture of geranial and neral) is commonly used in fragrances and flavors and is considered as a moderate allergen. Previous studies according to the local lymphnodeassay (LLNA)in micehaverevealed large variations in the sensitizing capacity of different geranial derivatives. Objectives: For a better understanding of these variations, a structure-activity relationship (SAR) study on a series of derivatives of geranial was carried out. Methods: The chemical reactivity of the compounds towards a model peptide was investigated using LC-MS. The adduct formation and the non-reacted peptide depletion were monitored. Adducts formed with model amino acids were investigated and structural determination was performed. Additional derivatives were synthesized and their sensitization potencies were evaluated in relation to their physicochemical and reactivity properties. Results: Most of the derivatives were shown to bind covalently to the cysteine residue of the model peptide. The percentage of depletion of the non-reacted peptide ranged from 0% to 100% after 24 hr, constant rate of depletion revealed a large difference between the fastest and lowest reacting derivatives. These resultswere congruent with the skin sensitization potencies obtained with the LLNA. Conclusions: A good correlation between the reactivity and the sensitizing potency was observed. Small changes in the chemical structure of geranial result in significant differences in sensitizing capacity and chemical reactivity. Conflicts of interest: The authors have declared no conflicts.

Ämnesord

NATURVETENSKAP  -- Kemi -- Annan kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Other Chemistry Topics (hsv//eng)

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

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