A wide variety of bacteria strains, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae are continuously emerging, causing a serious difficulty in the therapy of bacterial infections. Therefore, originally potent antimicrobial agents are now no longer exploitable, due to their weak or null activity towards these bacteria. In addition, during 2015 the new approved antibiotics are directed to old targets; this emergency prompted to the development of novel antibacterial drugs, possessing innovative mechanisms of action. In this context recently the essential cell division protein FtsZ (Filamentous temperature sensitive Z) turned to be an attractive target. FtsZ is widely conserved in several bacteria strains, it is homologue to mammalian beta-tubulin, which has been successfully exploited for cancer therapy, and its role in cell division revealed to be crucial. In the latest years, several compounds proved to interact with FtsZ and revealed to be selective antibacterial agents. Recently, we developed interesting derivatives, which antibacterial activities against MRSA strains reached MIC values in the range of 0.2–2.5 μg/mL. In addition, some lead compounds revealed also to be potent against Mycobacterium tuberculosis (Figure 1). The present work is intended to summing up the Structure Activity Relationship of this series of derivatives, which design started from 3-MBA (3-methoxy benzamide), DFNB (2,6-difluoro-3-nonyloxy benzamide), PC190723 and other previous optimized compounds (I, II).
|Titolo:||Structure Activity Relationship of novel antimicrobial agents, acting as inhibitors of the bacterial cell division protein Ftsz|
|Data di pubblicazione:||13-set-2016|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore BIO/19 - Microbiologia Generale
|Citazione:||Structure Activity Relationship of novel antimicrobial agents, acting as inhibitors of the bacterial cell division protein Ftsz / V. Straniero, C. Zanotto, L. Fumagalli, C. Bolchi, A. Radaelli, F. Bavo, M. Sanguinetti, C. De Giuli Morghen, M. Pallavicini. ((Intervento presentato al convegno New perspectives in medicinal chemistry tenutosi a Perugia nel 2016.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|