Molecular docking of ursolic acid and Staphylococcus aureus ATPase for antibacterial therapy

Maggi, Norbert; Schito, Anna Maria; Iobbi, Valeria; Bisio, Angela; Ruggiero, Carmelina

doi:10.1109/melecon48756.2020.9140570

Cited by 1 publication

(1 citation statement)

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“…Although the precise mechanisms underlying these findings are not known in detail, a study on the mode of action of UA against MRSA reported initial irreversible damage to bacterial membrane integrity, followed by inhibition of protein synthesis and the metabolic pathway [36]. Recently, by molecular docking, it has been hypothesized that UA can modulate the amount of ATP by inhibiting the hydrolysis of ATP (in MRSA) as polymyxins [37].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Ursolic Acid-Enriched Water-Soluble and Not Cytotoxic Nanoparticles against Enterococci

et al. 2021

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Ursolic acid (UA), a pentacyclic triterpenoid acid found in many medicinal plants and aromas, is known for its antibacterial effects against multi-drug-resistant (MDR) Gram-positive bacteria, which seriously threaten human health. Unfortunately, UA water-insolubility, low bioavailability, and systemic toxicity limit the possibilities of its application in vivo. Consequently, the beneficial activities of UA observed in vitro lose their potential clinical relevance unless water-soluble, not cytotoxic UA formulations are developed. With a nano-technologic approach, we have recently prepared water-soluble UA-loaded dendrimer nanoparticles (UA-G4K NPs) non-cytotoxic on HeLa cells, with promising physicochemical properties for their clinical applications. In this work, with the aim of developing a new antibacterial agent based on UA, UA-G4K has been tested on different strains of the Enterococcus genus, including marine isolates, toward which UA-G4K has shown minimum inhibitory concentrations (MICs) very low (0.5–4.3 µM), regardless of their resistance to antibiotics. Time-kill experiments, in addition to confirming the previously reported bactericidal activity of UA against E. faecium, also established it for UA-G4K. Furthermore, cytotoxicity experiments on human keratinocytes revealed that nanomanipulation of UA significantly reduced the cytotoxicity of UA, providing UA-G4K NPs with very high LD50 (96.4 µM) and selectivity indices, which were in the range 22.4–192.8, depending on the enterococcal strain tested. Due to its physicochemical and biological properties, UA-G4K could be seriously evaluated as a novel oral-administrable therapeutic option for tackling difficult-to-treat enterococcal infections.

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Section: Introductionmentioning

confidence: 99%