Síntese de acetanilidas e ésteres derivados de 4-hidroxichalconas : estudo de propriedades antimicrobiana, fluorescente e fotoprotetora

Abstract

Chalcones are simple to synthesize and have versatile applications, with relevance in both pharmaceutical and technological areas. Their unique molecular structure consists of α,β- unsaturated ketones linked by two aromatic rings, allowing electronic delocalization between them due to the presence of a conjugated double bond. This gives chalcones properties such as antimicrobial activity, luminescence and sun protection. In this work, twenty acetanilides derived from 4-hydroxychalcones were synthesized to investigate the effects of substituents on the arylenone and acetanilide moieties on their antimicrobial and fluorescent properties. In addition, ten new 4-esterchalcones, analogs of licochalcone, were strategically synthesized to study the effects of substituents on the arylenone moiety on their pharmacological and photoprotective properties. The final thirty compounds, twenty-eight of which were novel, were obtained with yields ranging from 60% to 89% and characterized by infrared (IR), 1H, 13C NMR and high-resolution mass spectrometry (HRMS) techniques. The ADME properties of the acetanilides and esters derived from 4-hydroxychalcones were evaluated, which demonstrated positive in silico characteristics for the development of new drug candidates. The acetanilide-chalcone 15c (R'=4'-OMe and R=4-Cl) demonstrated in vitro antimicrobial activity against strains of Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, with minimum inhibitory concentrations (MIC) ranging from 1.21 to 2.43 μmol mL−1. On the other hand, isovaleryl 4-esterchalcones showed antimicrobial activity against strains of S. aureus, Candida albicans and Candida tropicalis with MIC ranging from 2.64 to 3.32 μmol mL−1. It is also noteworthy that isobutyryl 4-esterchalcone 17d (4´-Br) exhibited antimicrobial activity against all strains tested, with MIC of 2.74 μmol mL−1. In the UV-Vis study of the ester derivatives, absorption λmax was identified around 312-327 nm, mainly in the UVB range. FPS-UVB tests demonstrated values ranging from 18.04 to 21.06, with high molar absorptivity coefficients (εmax). Isovaleryl 4-esterchalcone 16a (4´-H) stands out as the most promising, with a UVB SPF of 21.06, surpassing the commercial PABA filter. In the experimental photophysical studies, it was found that compounds 12e-15e (R´=4´-NO2) have intense photoluminescence in the solid state. Furthermore, when solubilized in a DMSO:water mixture, these materials showed a significant increase in fluorescence emission by the aggregation-induced emission enhancement (AIEE) phenomenon as the water proportion increased. Solvatochromic studies using the Lippert-Mataga and Rettig models were performed with four solvents. The best result was obtained for compound 15a with 4-Cl substituent, where the correlation coefficient R2 was 0.9. Compound 15a stood out for its high photoluminescence in the crystalline solid state, but did not demonstrate this property when the solid was ground, which suggests that it is a potential mechanofluorochrome (MFC). Additionally, in order to advance the creation of safer drugs and more environmentally friendly technological materials, a toxicity study using Artemia salina was conducted to evaluate the most promising compounds. The results suggest that some of the synthesized compounds may be promising for the creation of sunscreens with antimicrobial properties, as well as for the production of fluorescent dyes with smart applications.