Planejamento, síntese e aplicações de derivados naftosalicílicos como antioxidantes

Abstract

Salicylate derivatives are successfully applied as analgesics, antipyretics, anti-inflammatories and in cancer prevention, especially rectal colon. They reduce the risks of many diseases associated with elderly. However, adverse effects related to gastrointestinal events are always associated to its main constituent acetylsalicylic acid. These aspects are linked to their chemical stability and affinity for some biological receptors. The aims of this work are the design, synthesis and applications of naphthalene-salicylic derivatives as antioxidants. Thus, a theoretical study of the studied compounds was carried out. Calculations of electronic properties such as frontier orbitals HOMO-LUMO, ionization potential (IP), bond dissociation energy of phenolic moiety (BDEOH), and spin density contributions were performed by using density functional theory (DFT) at the B3LYP/6-31G (d, p) level of theory on Gaussview and Gaussian computational packages. Some of these compounds were synthesized by using classical methods. The theoretical results showed that both additional hydroxyl or substitution on benzene ring for naphthalene increase the antioxidant capacity in the same values with small dissimilarities among acid, ester, and amide derivatives. A synergistic effect was observed when both are used together, producing the most potent molecules. In addition, spin density calculations indicated a regioselective pathway can be gotten from monohydroxylic derivatives, with high possibility of in vivo generating of dihydroxy derivatives mainly at the para position relative to the phenolic group, through enzymatic or non-enzymatic reactions. Finally, the replacement of the naphthalene ring instead of the benzene ring increases both reactivity and chemical stability for the quinone-type intermediates, explaining how these compounds will play a role in the preventive mechanisms and way treatment of cancer. Anti cancer and anti-inflammatory activities are being performed for some of the synthesized compounds.