allowed direct interaction with the lipid ergosterol in membranes, leading to pore formation, membrane permeabilization, cell leakage, and eventual cell death (Ostrosky-Zeichner etal. 2010). However, recent investigations into structure–activ­ity relationships have revealed that polyenes actually form large extra- membranous aggregates, extracting vital membrane–lipid ergosterol from the plasma membrane. These challenges the previously held notion that channel formation is the primary mechanism of cell death (Amoretti etal. 2002; Perfect etal. 2010). The multifacto­rial nature of cell death is likely inuenced by ergosterol’s central role in various crucial cellular processes. In clinical settings, polyenes can cause major side effects such as systemic toxicity and nephrotoxicity due to structural similarities between ergosterol and the functional mammalian analog cholesterol in humans (Bencúrová et al. 2018; Duarte et al. 2019). To address these concerns, several lipid formulations of amphotericin B with enhanced safety proles have been developed and are exten­sively used to treat invasive and disseminated mycoses, which pose a serious threat to human life. Notably, adverse reactions to polyenes remain rare, even after years of use in the medical eld (Vincent etal. 2013).