Journal of Infectious Diseases and Treatment Open Access

Novel Sortase A inhibitors to counteract gram-positive bacterial biofilms

Joint Event on 6^th World Congress and Expo on Applied Microbiology & 8^th Edition of International Conference on Antibiotics, Antimicrobials & Resistance & 12^th International Conference on Allergy & Immunology

October 21-22, 2019 Rome, Italy

Maria Valeria Raimondi, Roberta Listro, Maria Grazia Cusimano, Mery La Franca, Teresa Faddetta, Giuseppe Gallo, Domenico Schillaci, Simona Collina, Ainars Leonchiks and Giampaolo Barone

University of Palermo, Italy University of Pavia, Italy APP Latvian Biomedical Research and Study Centre, Latvija

Scientific Tracks Abstracts: J Infec Dis Treat

Abstract:

Sortase A (SrtA) is a membrane enzyme responsible for the covalent anchoring of surface proteins on the cell wall of Gram-positive bacteria. Nowadays it is considered an interesting target for the development of new anti-infective drugs which aim to interfere with important Gram-positive virulence mechanisms. Along the years, we studied the anti-staphylococcal and anti-biofilm activity of some natural and synthetic polyhalogenated pyrrolic compounds, called pyrrolomycins. Some of them were active on Gram-positive pathogens at a μg/mL range of concentration (1.5-0.045 µg/mL) and showed a biofilm inhibition in the range of 50-80%. In light of these encouraging results, herein we present our efforts in the design and synthesis of novel pyrrolomycins. To dispose of sufficient amount for the in-depth in vitro investigation, we developed an efficient and easy-to-use microwave synthetic methodology. All compounds showed a good inhibitory activity toward SrtA, in accordance with the molecular modelling studies, having IC50 values ranging from 130 to 300 µM comparable to berberine hydrochloride, our reference compound. Particularly, the pentabromo-derivative exhibited the highest capability to interfere with biofilm formation of S. aureus with an IC₅₀ of 3.4 nM. This compound was also effective in altering S. aureus murein hydrolase activity, responsible for degradation, turnover, and maturation of bacterial peptidoglycan and involved in the initial stages of S. aureus biofilm formation.

Biography :

Maria Valeria Raimondi has completed her PhD in Pharmaceutical Science at the University of Palermo, Italy and Post-graduated Master in Drug Design and Development at University of Pavia, Italy. She has worked as a Visiting Scientist in Medicinal Chemistry at University of Hamburg-Fakulta�?�?t MIN-Fachbereich Chemie-Organische Chemie. She works as an Assistant Professor in Medicinal Chemistry at University of Palermo, Italy. She is a Lab Chief for Laboratory of Synthesis of Heterocyclic Compounds with Potential Biological Activity at University of Palermo, Italy, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies. She has published more than 40 papers in international peer-reviewed journals.