Photoresponsive Prodrugs of Butyric Acid Based on Amino Naphthopyranones

The use of pharmacologically inert derivatives as a means to overcome common drawbacks associated with the intake of drugs (i.e. low oral absorption, chemical instability or toxicity) has increased the interest in the development of efficient prodrugs [1]. Photoresponsive prodrugs have been proposed recently for the optimisation of drug delivery as the use of light as triggering agent allows spatial and temporal control of the release process [2]. In this communication we report the synthesis of ester conjugates of butyric acid, a short chain fatty acid involved in the regulatory mechanisms for gene expression known to promote markers of cell differentiation, apoptosis and cell growth control. Given our interest in the design of novel photolabile protecting groups based on oxygen heterocycles [3], the esters were prepared by reaction with several amino naphthopyranones, in order to evaluate the differences in the photolytic release of butyric acid from the heterocyclic cages. Photolysis studies were carried out under irradiation at different wavelengths (250, 300, 350 and 419 nm) in a Rayonet RPR-100 photochemical reactor in mixtures of organic solvent and HEPES buffer solution in a 80:20 proportion. [1] Dahan, A.; Khamis, M.; Agbaria, R.; Karaman, R. Expert Opin. Drug Del. 2012, 9, 1001-1013. [2] Fomina, N.; Sankaranarayanan, J.; Almutairi, A. Adv. Drug Deliver. Rev. 2012, 64, 1005-1020. [3] a) Piloto, A. M.; Soares, A. M. S.; Costa, S. P. G.; Gonçalves, M. S. T. Amino Acids, 2012, 42, 2275-2282. b) Piloto, A. M.; Soares, A. M. S.; Hungerford, G.; Costa, S. P. G.; Gonçalves, M. S. T. Eur. J. Org. Chem. 2011, 5447-5451.