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Volume 05
Journal of Infectious Diseases and Treatment
ISSN: 2472-1093
JOINT EVENT
Applied Microbiology-2019 & Antibiotics 2019
Immunology 2019
October 21-22, 2019
October 21-22, 2019 Rome, Italy
&
&
8
th
Edition of International Conference on
Antibiotics, Antimicrobials & Resistance
12
th
International Conference on
Allergy & Immunology
6
th
World Congress and Expo on
Applied Microbiology
Novel Sortase A inhibitors to counteract gram-positive bacterial biofilms
Maria Valeria Raimondi
1
, Roberta Listro
2
, Maria Grazia Cusimano
1
, Mery La Franca
1
, Teresa Faddetta
1
, Giuseppe Gallo
1
, Domenico Schillaci
1
, Simona
Collina
2
, Ainars Leonchiks
3
and
Giampaolo Barone
1
1
University of Palermo, Italy
2
University of Pavia, Italy
3
APP Latvian Biomedical Research and Study Centre, Latvija
S
ortase 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 IC
50
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 IC
50
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-Fakultät 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.
Maria Valeria Raimondi et al., J Infec Dis Treat 2019, Volume: 05