Gram-positive bacteria are a significant cause of nosocomial and community-acquired infections associated withdiseases of high morbidity and mortality. Moreover, antibiotic resistance of important Gram-positive pathogens,such as Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis is one of the major worldwidehealth problems. Over the last decade, many studies have focused on agents that target the virulence ofimportant pathogens without killing or inhibiting their growth therefore imposing limited selective pressure topromote the development and spread of resistance mechanisms enterococci and streptococci, sortase A plays acritical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the developmentof new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such asadhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase Aas an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located onthe cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing theview that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have beenidentified to date using high-throughput or in silico screening of compound libraries (synthetic or natural.We synthesized two classes of molecules: curcumin analogues and N-phenyl-1H-pyrazole-4-carboxamides ableto interfere with the bacterial adhesion, a fundamental step of Gram-positive pathogenesis .All derivatives obtained were tested for both the planktonic growth inhibition activity and the inhibition of biofilmformation against the following reference bacterial strains: S. aureus ATCC 6538, S. aureus ATCC 25923and S. aureus ATCC 29213.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2015|