Síntese, caracterização, análises conformacional e atividade biológica de 2’, 3’ e 4’ – bromochalconas

Abstract

The chalcones are associated to several biological activities, among which we can mention: antioxidant, antiallergic, anti-inflammatory, anticarcinogenic, antiulcerogenic, vasodilator, antispasmodic, antiplatelet, antimicrobial and antiviral. The molecular modification of chemical structures is one of the tools most used by the pharmaceutical industry to obtain new drugs, within this context it was interesting to synthesize four chalcones, one of them without substituent in the aromatic rings, comparing it with chalcones that present the atom of bromine in structure. Evaluating also the positioning of this substituent in the ring as a comparative character. Thus, in this work we demonstrate the synthesis and characterization by NMR of ¹H and ³³C of the following chalcones: 1-Phenyl-2-propen-3-phenyl-1-one (CHAL), 1- (2-Bromophenyl) -2-propene -3-phenyl-1-one (m-CHALBr) and 1- (4-Bromophenyl) -2-propenecarboxylate (oCHALBr), 1- (3-Bromophenyl) -2-propen- -3-phenyl-1-one (p-CHALBr). All were obtained in satisfactory yield and purity by condensation of Claisen-Schmidt, using benzaldehyde and acetophenone derivatives. In addition, these chalcones were evaluated with respect to their antimicrobial and antioxidant activity. In the tests performed for the evaluation of antimicrobial activity, the chalcone without substituent showed activity against Gram positive species, this activity was slightly increased by the presence of bromine in the ortho position, while the presence of this halogen at the meta position maintained the activity only against S. aureus species. The bromo in the para position, apparently impaired the antimicrobial activity. The evaluation of the antioxidant activity presented positive results for the four chalcones. The chalcone without substituent presented antioxidant activity, which can be overcome, in certain concentrations, replacing bromine in the ortho position. However, the substitution of bromo in the meta positions and for apparently decreases the antioxidant activity. To complement, a conformational study of the compounds was carried out using theoretical calculations, which were developed with the theory level HF / 6-31G for the scan calculations, M06- 2X / 6311 ++ G (2d, 2p) for the optimizations and frequencies, determining the energies and geometries, and also M06-2X / 6-311 ++ G (2d, 2p) for the NBO calculations, determining the hyperconjugative effects of the compounds. The program package used was GAUSSIAN 09. The programs PyMOL and GaussView 5 are used for the visualization of structures and surfaces. At the end of these calculations, it was possible to confirm that the conformation of greater stability for all the studied compounds presented the carbonyl and the vinyl double bond arranged in s-cis manner. As the hyperconjugative effect was responsible for the largest population of s-cis versus s-trans.