Banca de DEFESA: MELISSA FARIAS ALVES DA SILVA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : MELISSA FARIAS ALVES DA SILVA
DATE: 09/05/2024
TIME: 14:00
LOCAL: Videoconferencia - Link para acesso: https://meet.google.com/pkb-hpvq-sqe
TITLE:

PROSPECTION OF ANTIFUNGAL ACTIVITY AND MODULATORY POTENTIAL OF EXTRACTS AND FRACTIONS OF Tephrosia toxicaria (Sw.) Pers in REFERENCE ANTIMICROBIALS

KEY WORDS:

Natural products. Antifungal Therapy. Mycoses. Synergy.

PAGES: 136
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Fungal infections represent a major contributor to the increasing global mortality rate associated with infectious diseases. This increase is largely attributed to the indiscriminate use of antibiotics and antifungals agents, whose effectiveness is compromised by the development of resistance in pathogens and the adverse effects observed in non-target organisms. Botanical extracts and their fractions have been highlighted as promising sources for the development of antifungals and therapeutic adjuvants for reference drugs as they are derived from renewable sources and present toxic selectivity. Tephrosia toxicaria (Sw.) Pers, a legume well adapted to the northeastern semi-arid region, has stood out for its biopotential. The present research aimed to investigate the antifungal potential of extracts and protein fractions obtained from T. toxicaria seeds against species of the Candida and Cryptococcus genera and their modulating activity for reference antimicrobials. The extracts and fractions obtained by the Scopes and Osborne methods were partially biochemically characterized and evaluated for their antifungal activity by determining the MICs (Minimum Inhibitory Concentration). Subsequently, the most active fraction and its combinations were also investigated regarding their possible mode of action. The extracts and fractions showed antifungal activity to different degrees for at least one of the yeasts tested, in which the T 50-75 fraction was the most active against Cryptococcus gattii, Cryptococcus neoformans and Candida parapsilosis and the GLB fraction against Candida albicans. The lowest MIC₁₀₀ values (MIC, capable of inhibiting 100% of growth) found were 32 µg/mL for the T 50-75 fraction against Cryptococcus gattii (R-265), 128 µg/mL for the ST extract and 256 µg/mL for fractions T 50-75 and T 75-100, all against C. gattii (FC1). The ST extract and the fractions T 50-75 and T 75-100, as they presented the lowest MIC₁₀₀ values, were selected to investigate their modulating potential in combination with Amphotericin B, Fluconazole and 5-Flucytosine, using the association method (checkerboard) by FICI (Fractional Inhibitory Concentration Index) and by mathematical models (Blis, HSA, Loewe and ZIP). All tested combinations were able to reduce the MIC₁₀₀ for C. gattii and after data harmonization, the combinations between the T 50-75 and T 75-100 fractions with Amphotericin B and Fluconazole were classified as synergistic, however the combinations with the fraction T 50-75 showed greater sensitivity (93%) and degree of synergistic intensity. The combination of the fraction T 50-75 with the drugs caused greater interference in the growth curve, melanization and a significant reduction in capsule size. However, exposure of C. gattii to treatment with only the T 50-75 fraction also caused morphological changes in the cell wall and capsule, indicating that the fraction contributed strongly to the result observed in combination with the drug. Therefore, the T 50-75 fraction presents itself as a promising candidate for the development of adjuvants and/or new drugs for antifungal chemotherapy. Analysis of the results suggests that the fungistatic action of the T 50-75 fraction can contribute to minimizing the emergence of resistance in the pathogen, acting in redundant pathways and reducing the effective concentrations of clinical reference drugs, thus improving treatment and minimizing toxicity generated.

COMMITTEE MEMBERS:
Externo à Instituição - GABRIEL BONAN TAVEIRA - UENF
Presidente - 1549705 - ADRIANA FERREIRA UCHOA
Interna - 1453487 - KATIA CASTANHO SCORTECCI
Externo à Instituição - THALES DOMINGOS ARANTES - UFG