New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrrolomycins in good yields and in suitable amount for their in vitro in-depth investigation. We evaluate the inhibitory activity towards Sortase A (SrtA), a transpeptidase responsible for covalent anchoring in Gram-positive peptidoglycan of many surface proteins involved in adhesion and in biofilm formation. All compounds show a good inhibitory activity toward SrtA, having IC50 values ranging from 130 to 300 µM comparable to berberine hydrochloride. Of note compound 1d shows a good affinity in docking experiment to SrtA and exhibits the highest capability to interfere with biofilm formation of S. aureus showing an IC50 of 3.4 nM. This compound is also effective in altering S. aureus murein hydrolase activity that is known to be responsible for degradation, turnover, and maturation of bacterial peptidoglycan and involved in the initial stages of S. aureus biofilm formation.

Raimondi, M.V., Listro, R., Cusimano, M.G., La Franca, M., Faddetta, T., Gallo, G., et al. (2019). Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action. BIOORGANIC & MEDICINAL CHEMISTRY, 27(5), 721-728 [10.1016/j.bmc.2019.01.010].

Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action

Raimondi, Maria Valeria;Cusimano, Maria Grazia;La Franca, Mery;Faddetta, Teresa;Gallo, Giuseppe;Schillaci, Domenico;Barone, Giampaolo
2019-01-01

Abstract

New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrrolomycins in good yields and in suitable amount for their in vitro in-depth investigation. We evaluate the inhibitory activity towards Sortase A (SrtA), a transpeptidase responsible for covalent anchoring in Gram-positive peptidoglycan of many surface proteins involved in adhesion and in biofilm formation. All compounds show a good inhibitory activity toward SrtA, having IC50 values ranging from 130 to 300 µM comparable to berberine hydrochloride. Of note compound 1d shows a good affinity in docking experiment to SrtA and exhibits the highest capability to interfere with biofilm formation of S. aureus showing an IC50 of 3.4 nM. This compound is also effective in altering S. aureus murein hydrolase activity that is known to be responsible for degradation, turnover, and maturation of bacterial peptidoglycan and involved in the initial stages of S. aureus biofilm formation.
2019
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/19 - Microbiologia Generale
Settore CHIM/03 - Chimica Generale E Inorganica
Raimondi, M.V., Listro, R., Cusimano, M.G., La Franca, M., Faddetta, T., Gallo, G., et al. (2019). Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action. BIOORGANIC & MEDICINAL CHEMISTRY, 27(5), 721-728 [10.1016/j.bmc.2019.01.010].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/339458
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