Maria Valeria Raimondi1, Alessandro Presentato2, Giovanna Li Petri1, Miriam Buttacavoli2, Agnese Ribaudo1,3, Viviana De Caro1, Rosa Alduina2, Patrizia Cancemi2. 1. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, Italy. 2. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, viale delle Scienze, Building 16, 90128 Palermo, Italy. 3. Pharmaceutical Department, Provincial Health Authority (ASP) of Palermo, via Pindemonte 88, 90129 Palermo, Italy.
Abstract
: Pyrrolomycins (PMs) are polyhalogenated antibiotics known as powerful biologically active compounds, yet featuring high cytotoxicity. The present study reports the antibacterial and antitumoral properties of new chemically synthesized PMs, where the three positions of the pyrrolic nucleus were replaced by nitro groups, aiming to reduce their cytotoxicity while maintaining or even enhancing the biological activity. Indeed, the presence of the nitro substituent in diverse positions of the pyrrole determined an improvement of the minimal bactericidal concentration (MBC) against Gram-positive (i.e., Staphylococcus aureus) or -negative (i.e., Pseudomonas aeruginosa) pathogen strains as compared to the natural PM-C. Moreover, some new nitro-PMs were as active as or more than PM-C in inhibiting the proliferation of colon (HCT116) and breast (MCF 7) cancer cell lines and were less toxic towards normal epithelial (hTERT RPE-1) cells. Altogether, our findings contribute to increase the knowledge of the mode of action of these promising molecules and provide a basis for their rationale chemical or biological manipulation.
: Pyrrolomycins (n class="Chemical">PMs) are polyhalogenated antibiotics known as powerful biologically active compounds, yet featuring high cytotoxicity. The present study reports the antibacterial and antitumoral properties of new chemically synthesized PMs, where the three positions of the pyrrolic nucleus were replaced by nitro groups, aiming to reduce theircytotoxicity while maintaining or even enhancing the biological activity. Indeed, the presence of the nitro substituent in diverse positions of the pyrrole determined an improvement of the minimal bactericidal concentration (MBC) against Gram-positive (i.e., Staphylococcus aureus) or -negative (i.e., Pseudomonas aeruginosa) pathogen strains as compared to the natural PM-C. Moreover, some new nitro-PMs were as active as or more than PM-C in inhibiting the proliferation of colon (HCT116) and breast (MCF 7) cancer cell lines and were less toxic towards normal epithelial (hTERT RPE-1) cells. Altogether, our findings contribute to increase the knowledge of the mode of action of these promising molecules and provide a basis for theirrationale chemical or biological manipulation.
Authors: Saúl Noriega; Jaime Cardoso-Ortiz; Argelia López-Luna; Ma Del Refugio Cuevas-Flores; Juan Armando Flores De La Torre Journal: Pharmaceuticals (Basel) Date: 2022-06-05
Authors: Giovanna Li Petri; Maria Valeria Raimondi; Virginia Spanò; Ralph Holl; Paola Barraja; Alessandra Montalbano Journal: Top Curr Chem (Cham) Date: 2021-08-10