Considerations Regarding the Cytotoxicity of Certain Classes of Fungal Polyketides-Potential Raw Materials for Skincare Products for Healthy and Diseased Skin.

: This study investigates the cytotoxicity of microbial polyketides biosynthesized by species through both in silico and in vitro approaches. : Six main know -derived polyketides were analysed in silico an an vitro. : In silico tests reveal that the main derived compounds exhibit lipophilic properties, indicating their potential suitability as active ingredients in dermato-cosmetic formulations. In silico tests revealed significant flexibility and high degrees of unsaturation for some -derived polyketides, suggesting a broad interaction potential and a propensity for chemical instability. In silico permeability tests indicated low epidermal penetration. Cytotoxicity assays conducted in vitro on a HaCaT cell line revealed varying levels of cytotoxicity among the three classes of fungal polyketides. Yellow polyketides derived from and exhibited moderate cytotoxicity, while orange polyketides derived from the same strains showed low cytotoxicity. Red, orange, and yellow polyketides derived from a high-productive sp. genus showed low or negligible cytotoxicity. After 48 h of exposure, the cytotoxic profiles of all polyketides remained relatively stable. The IC values obtained through linear or nonlinear models supplied by EXCEL MS Office or for the Systat programme indicated moderate-to-low cytotoxicity for polyketides derived from and . The bioproducts derived from high-productive sp. exhibited weak or negligible cytotoxicity. : The results obtained suggest that the -derived polyketides possess promising properties for therapeutic and cosmetic applications, but their chemical stability must be considered in the case of dermatological formulations.