Study of the action of metabolites produced by fungi in an in vitro wound microenvironment

Abstract

Fungi are sources of a wide diversity of secondary metabolites that can present distinct pharmacological properties and potential for pharmaceutical use. Among these compounds, a few species are able to produce alpha-pyrone derivatives as annularins with cytotoxicity and antimicrobial activity. In a previous study performed by our group, an annularin derivative showed action on the repair and epithelial remodeling in the healing process of skin wounds. Continuing the previous study, this proposal aims to obtain alpha-pyrones produced by two species of fungi and evaluate their activity in an in vitro wound microenvironment. The compounds will be obtained by fungal culture, liquid-liquid extraction, and purification by high-performance liquid chromatography (HPLC). The healing action of pure and structurally characterized compounds will be evaluated in a two-dimensional (2D) and in a three-dimensional (3D) microfluidic biomimetic model of the wound. Parameters involved in the repair of the injured area, such as cell migration and proliferation, formation of reactive oxygen species (ROS), participation of intracellular signaling pathways, cell-cell interaction, formation of the vascular network, differentiation of fibroblasts to myofibroblasts and protein synthesis of the extracellular matrix (ECM) will be evaluated. The results are expected to indicate the prospect of pharmaceutical application of new alpha-pyrone derivatives, for example, in cases of diabetic wounds or wounds associated with biofilms. (AU)