Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds

0577714 - ÚOCHB 2024 RIV CH eng J - Journal Article
Šebek, V. - Anzenbacher, P. - Rejman, Dominik - Špičáková, A. - Kolář, M.
Lipophosphonoxins—A Novel Group of Broad Spectrum Antibacterial Compounds.
Pharmaceutics. Roč. 15, č. 10 (2023), č. článku 2395. E-ISSN 1999-4923
R&D Projects: GA MŠMT(CZ) LX22NPO5103; GA ČR(CZ) GA22-08857S
Institutional support: RVO:61388963
Keywords : lipophosphonoxin * antibiotics * resistance * LPPOs * antimicrobial resistance
OECD category: Microbiology
Impact factor: 5.4, year: 2022
Method of publishing: Open access
https://doi.org/10.3390/pharmaceutics15102395

Lipophosphonoxins (LPPOs) represent a new group of membrane-targeting antibiotics. Three generations of LPPOs have been described: First-generation LPPOs, second-generation LPPOs, and LEGO-LPPOs. All three generations have a similar mode of bactericidal action of targeting and disrupting the bacterial cytoplasmic membrane of prokaryotic cells, with limited effect on eukaryotic cells. First-generation LPPOs showed excellent bactericidal activity against Gram-positive species, including multiresistant strains. Second-generation LPPOs broaden the antibiotic effect also against Gram-negative bacteria. However, both first- and second-generation LPPOs lose their antibacterial activity in the presence of serum albumin. LEGO-LPPOs were found to be active against both Gram-positive and Gram-negative bacteria, have better selectivity as compared to first- and second-generation resistance to LEGO-LPPOs was also not observed, and are active even in the presence of serum albumin. Second-generation LPPOs have been studied as antimicrobial additives in bone cement and as nanofiber dressing components in the treatment of wound infections in mice. Second-generation LPPOs and LEGO-LPPOs were also tested to treat ex vivo simulated endodontic infections in dental root canals. The results of all these studies were encouraging and suggested further investigation of LPPOs in these indications. This paper aims to review and compile published data on LPPOs.
Permanent Link: https://hdl.handle.net/11104/0346830