Banca de DEFESA: CAROLINA DO ROSÁRIO ESTEVES GUIMARÃES

EVALUATION OF MOLECULES WITH EFFECT ANTIBIOFILM FOR Candida albicans

Antibiofilm. Candida albicans. Thiosemicarbazones. Natural products.

Biofilms are highly organized communities of microorganisms that are less susceptible to antimicrobials than planktonic cells. Their development comprises one of the main virulence factors of Candida albicans, one of the most isolated and studied species in infections caused by Candida sp. When associated with biofilms, the treatment of these infections becomes more complicated due to the need for higher concentrations of antifungals than those required in infections caused by planktonic cells. Thus, therapeutic choices, which are limited, require new alternatives, of which biofilm inhibition and eradication appear to be promising strategies. Molecules with antibiofilm activity have been studied, but without taking care to use important criteria such as inhibition concentration of biofilm formation lower than the antifungal concentration and concentrations equal to or lower than 300 µM. In this sense, the aim of our study was to evaluate molecules with an antibiofilm effect on C. albicans, through a review of molecules described in the literature from 2011-2021 and the experimental analysis of two sets of molecules, one of thiosemicarbazones and analogues and the other of derivatives of natural products. In the literature review we discussed 21 articles, which described 42 molecules. Most of the molecules showed promise for inhibiting biofilm formation and had mechanisms of action that included changes in the adhesion process, yeast-hyphae transition, hyphae elongation, cell surface hydrophobicity and the production of quorum sensing components. These results guided the experimental part of the work, as well as the choice of some of the molecules tested. For the set of thiosemicarbazones and analogues innovated in the review, molecule 28 stood out for its greater potency in inhibiting biofilm formation by 50% (BIC50 = 31.55 ± 1.18 µM). For derivatives of natural products with chemical groups similar to those described in the review, molecule 6, identified as jatrophone, stood out for its greater inhibition power (BIC50 = 64.36 ± 1.05 µM) and ability to eradicate biofilms (BEC50 = 215.90 ± 1.07 µM). Scanning electron microscopy (SEM) studies showed that both molecules reduced the number of adhered cells, hyphae and pseudohyphae formed after exposure to BIC50, while jatrophone reduced the formation of hyphae in preformed biofilm in the presence of BEC50. Thus, we were able to determine the family of thiosemicarbazones and analogues, as well as jatrophone, as models for future studies that will allow us to further elucidate the mechanism of action of these molecules on the biofilm and optimise their structure to increase potency and selectivity.