Banca de QUALIFICAÇÃO: MELISSA FARIAS ALVES DA SILVA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MELISSA FARIAS ALVES DA SILVA
DATE: 22/03/2024
TIME: 09:00
LOCAL: Videoconferencia - https://meet.google.com/tuc-zatf-qqj
TITLE:

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

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 growing global mortality rate associated with infectious diseases. This increase is largely attributed to the indiscriminate use of antibiotics and antifungal 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 therapeutic adjuvants as they are derived from renewable sources and exhibit toxic selectivity. In previous work, our group described the leishmanicidal, larvicidal and antibacterial activity of extracts obtained from different organs and vegetative organs of Tephrosia toxicaria (Sw.) Pers, a legume well adapted to the northeastern semi-arid region. 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 with reference antimicrobials. The best conditions for extraction and obtaining of fractions (resulting from classic Scopes and Osborne protein fractionation methods) were evaluated for their antifungal activity, resulting in the determination of MIC (Minimum Inhibitory Concentration). The most active MIC were selected for investigation regarding their modulating potential in combination with Amphotericin B, Fluconazole and 5-fluconazole through the association method (checkerboard) by FICI (Fractional Inhibitory Concentration Index) and by mathematical models (Blis, HSA, Loewe and ZIP), in addition to determining the possible mode of action, toxicity and initial biochemical characterization. The most active MIC were determined for the T50-75 fraction (32 µg/mL) against the standard strain of Cryptococcus gattii (R-265), and 128 and 256 µg/mL for the ST extract and the T 50-75 fraction , respectively, on the multi-resistant clinical strain of C. gattii (VGII). All combinations tested were able to reduce the lethal dose (LC100, capable of inhibiting 100% of growth) for yeast. After data harmonization, the independent combinations between the T50-75 and T75-100 fractions with Amphotericin B and Fluconazole were classified as synergistic, however the combinations with the T50-75 fraction showed greater sensitivity (93%) and degree of synergistic intensity. The interference of the combination of the T50-75 fraction with antimicrobial drugs on the growth curve associated with the morphological changes observed in C. gattii, such as interference with melanization and reduction in capsule size, indicate that the T50-75 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 T50-75 fraction can contribute to minimizing the emergence of resistance in the pathogen, acting on redundant pathways and reducing the effective concentrations of clinical reference drugs, thus improving treatment and minimizing toxicity.

COMMITTEE MEMBERS:
Interno - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Externa à Instituição - KÁSSIA JÉSSICA GALDINO DA SILVA SCHINAIDER
Presidente - 1997012 - RAQUEL CORDEIRO THEODORO