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Exploring the anticancer activity and the mechanism of action of pyrrolomycins F obtained by microwave-assisted total synthesis

  • Autori: Barreca, Marilia; Buttacavoli, Miriam; Di Cara, Gianluca; D'Amico, Cesare; Peri, Emanuela; Spano', Virginia; Li Petri, Giovanna; Barraja, Paola; Raimondi, Maria Valeria; Cancemi, Patrizia; Montalbano, Alessandra
  • Anno di pubblicazione: 2023
  • Tipologia: Articolo in rivista
  • OA Link:


Pyrrolomycins (PMs) are a family of naturally occurring antibiotic agents, isolated from the fermentation broth of Actinosporangium and Streptomyces species. Pursuing our studies on pyrrolomycins, we performed the total synthesis of the F-series pyrrolomycins (1–4) by microwave-assisted synthesis (MAOS), thus obtaining the title compounds in excellent yields (63–69%). Considering that there is no evidence so far of the anticancer effect of this class of compounds, we investigated PMs for their antiproliferative activity against HCT116 and MCF-7 cancer cell lines. PMs showed anticancer activity at submicromolar level with a minimal effect on normal epithelial cell line (hTERT RPE-1), and they were able to induce several morphological changes including elongated cells, cytoplasm vacuolization, long and thin filopodia as well as the appearance of tunneling nanotubes (TNTs). These data suggest that PMs could act by impairing the cell membranes and the cytoskeleton organization, with subsequent increase of ROS generation and the activation of different forms of non-apoptotic cell death.