Read Aloud the Text Content
This audio was created by Woord's Text to Speech service by content creators from all around the world.
Text Content or SSML code:
Good afternoon, thank you all for coming. Today I am going to present my current experiment with the title: “Potential antifungal activity of flavones in combination therapies”, this is part of a collaboration between our group and a research group from the University of Graz. The presentation consists of the following parts. Introduction, Objectives, Methodology used, Results, Conclusion and References. Invasive fungal infections are an increasing problem worldwide, contributing to 1.6 million deaths annually and are an important cause of human mortality and morbidity, particularly for immunocompromised populations. Currently, there are only 4 types of antifungals used in clinic, and many fungal species are resistant to these drugs or are partially effective. Due to this, it is urgent to develop new strategies to combat fungal infections, and there are several strategies such as use of combination therapies, discovering new drugs OR natural compounds with possible antifungal activity alone or in synergistic combinations to overcome the problem with resistance. The use of natural compound like phenolic compounds is an excellent approach to reduce the side effects and toxicity. Phenolic compounds are bioactive phytochemicals that include multiple subclasses, one of these most studied groups of these compounds is flavonoids. These compounds are widely distributed in plants, such as fruits, vegetables, herbs, spices, and certain beverages (like tea, coffee, and wine). The flavonoids can be sub-divided in different groups. Among them, flavones and flavonols define the largest subgroups. The subgroup that interests us in this experiment are flavones, which have been reported different biological activities as antioxidant, anti-inflammatory, antimicrobial, antiviral activities, among others. In addition to these biological activities, flavones have shown antifungal activity against yeasts and filamentous fungi in different studies, how it shown in next slide, where different studies demonstrate antifungal activity of flavonoids in general or specifically flavone. Furthermore, Gratz's group also observed that some flavones such as F42 have activity against C. glabrata and C. albicans So, in this context, our group in collaboration with a team from the University of Graz in Austria, we want to identify flavones compounds with antifungal potential in combination with standard antifungals drugs, specifically the azoles. To carry out our goal, we first analyzed the effect of these compounds in vitro, using the Checkerboard assay with different fungal genera to determine the best candidate for antifungal combinations. And then later, animal experiments will be carried out. In this seminar I am going to show results we have obtained with the compound 3,6 dihydroxyflavone, abbreviated as F42. Therefore, the objective of this present experiment is to determine in vitro antifungal activity of F42 alone or in combination with the azoles against clinically relevant fungi. To determine interaction of F42 compounds with azoles, checkerboard assay based on CLSI microdilution technic were performed. Briefly, F42 and different azoles are diluted in series, using a dilution of two-factor and are distributed in a 96-well microplate and added in 1:1 volume. In the first column and last row, we are added F42 and azoles alone respectively. The data obtained were analyzed using the model-fractional inhibitory concentration index (FICI): An FICI value of ≤0.5 was interpreted as synergy whereas the FICI values between 0.5 and 1.0 were interpreted as additive. FICI values >4.0 were considered as antagonism and FICI values between 1.0 and 4.0 were considered as indifferent, following a conservative approach. Next, I’m going to explain results we have obtained. The graph represents the FICI index of different fungal strains. In this study, we tested yeasts like Candida glabrata, auris and albicans, and filamentous fungi like Aspergillus fumigattus, Scedosporuim apiospermum and Fusaruim solani. Red dashed line denotes the cutoff FIC index of 0.5 for synergistic interaction. As can be seen in the graph, F46 combined with VRC showed a synergistic effect against 8/19 (represents more than 42%) strains tested, with the effect being observed mainly in 3/4 (75%) of the C. albicans strains. While in C. auris and A fumigatus strains the combination was synergistic in two strains tested. In the case of C. glabrata and F. solani synergism was only observed in one strain. No synergy was observed in Solani strains. The combination of F46 and VRC had higher synergistic effect compared to other combinations. F46 + PSC had effect against 7/19 (36.8%) strains tested. Half (50%) of the C. albicans and C. auris strains shown synergistic effect. The combination had no synergistic effects on Scedosporium apiospermum and neither on two Aspegillus strains out of three totals tested. Finally, no synergistic effect has been observed when combined F42 with FCZ, drug interaction shows indifference in most strains. In the next seminar, I hope to present you results on another flavone compound.