Bioprospecção de novos compostos monocurcuminoides sintéticos: atividade antioxidante, antimicrobiana e sinérgica e avaliação da citotoxicidade “in vitro”

Abstract

As a consequence of the improper and/or exarcerbated use of medications, infections such as the ones caused by microorganisms are emerging as a critical health problem considering that conventional strategies are no longer satisfactory for the treatment of these diseases. As a result, the search for the development and characterization of new compounds with biological activity is an obstacle for researchers. Natural compounds are emerging as a safe and accessible alternative for the study bioactive compounds. Curcumin is extracted from the spice turmeric, the power dried rhizome Curcuma longa (Zingiberaceae). However due to its lipophilic nature curcumin’s bioavailability is low, affecting its efficiency in the organism. Studies regarding structural modifications allow new prospective bioactive molecules. New candidates are presented as monocurcuminoids (CN’s) and are based on curcumin’s chemical structure with only one methyl bridge. The study was conducted with four previously synthetized CN’s (59, 63, 67 and 77) along with curcumin (SIGMA) and turmeric powder (POWDER). Chemical identification of SIGMA and POWDER was performed with GC-MS and showed similar peaks, indicating a possible presence of curcumin in turmeric powder. Antioxidant activity was evaluated by DPPH and ABTS assays. Compounds showed similar values to vitamin c for the ABTS scavenging capacity. MIC values were evaluated in different strains (ATCC and clinical isolates) and presented values between 4.06 and 150µg/ml. Only for S. aureus MIC and MBC were equal when treated with CN 63 and 67 with values of 150 and 120µg/ml, respectively. Synergistic effect of CN 77 with POWDER was observed for A. hydrophila, C. albicans and P. aeruginosa, when treated with 8.75 and 4.37µg/ml of CN 77 and 9.37 and 4.68µg/ml of POWDER. Photodynamic therapy was effective in 2x MIC of CN 59 for E. faecalis with growth inhibition by 4.18-fold and on E. coli the same treatment almost abolished bacterial growth. Hemolytic cytotoxicity showed safe intervals for all compounds, with IC50 values ranging from 49.65 to 130.9µM. Anticoagulant activity demonstrated values within range for most compounds when compared to warfarin but when compared with heparin most values were above the recommended interval, indicating a possible anticoagulant activity for the intrinsic pathway. Taking together, the results showed that CN’s are safe and a promising alternative for curcumin.