State University of Maringa, Brazil
Title: New antifungal designed by biotechnology and bioinformatics approaches
Terezinha Svidzinski has experience in the areas of laboratorial diagnostics and antifungals used in the treatment of invasive fungal infections. She serves as Professor and Head of the Medical Mycology group, at State University of Maringá, Paraná, Brazil, which mainly focuses on the interface between human health and fungal diseases and the development of new antifungal drugs. She has academic experience as advisor and on articles published in her field of interest.
Statement of the Problem: Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients worldwide in recent decades. Specially the fungal healthcare–associated or nosocomial fungal infections. According to Global Action Fund for Fungal Infections over 1 billion people worldwide are affected and 25 million patients are at imminent risk of death due to fungal infections. The mortality due to IFIs is too high, ranging from 30 to 60%, reality that has been attributed mainly to treatment failure. The purpose of this study is to describe our experience with new small molecules, selected by in silico methodology, regarding their in vitro and in vivo antifungal properties. Methodology & Theoretical Orientation: Our group, in collaboration with other researchers experts in biotechnology and bioinformatics have developed studies exploring the interaction of small molecules with specific fungal target receptors. Currently some new molecules were already selected and they are promising candidates to the development of new antifungal drugs. Thus, they have been evaluated considering their mycological aspects against some important human pathogenic fungi. Findings: These compounds showed antifungal activity individually on Candida spp, including C. glabrata and C. krusei, both species non-responsive to fluconazole; also against Cryptococcus spp and Paracoccidioides spp, fungi responsible for systemic mycoses, difficult management and with high mortality rates. Besides, some of these molecules have showed synergistic effect with usual antifungals. Conclusion & Significance: We were able to demonstrate lower minimum fungicidal concentration of these molecules, as well as inhibition of some fungal virulence factors. Besides, they are toxicologically inert in vitro and showed low toxicity in animal model, and also they were able to reduce experimental systemic infections in mice. Therefore, in silico methods have been an important tool for new antifungal design, decreasing cost and accelerating the antifungal development process.