Effect of ether groups on the Structure Activity Relationship (SAR) of novel antimicrobial compounds.

摘要

Bacterial resistance to antibiotic treatment has become a major problem over the years originating from penicillin binding proteins, efflux pumps and the major contributor, beta-lactamases. Therefore, a need arises for developing new antimicrobial drugs, with a different mechanism of action, in-order to delay further bacterial resistance. Examples of such compounds prepared in our research group comprise of monocyclic beta-lactams with distinct substituent groups attached to an aromatic thiol, at the C4 of the beta-lactam. These compounds, especially fluorinated thiophenols in the ortho position with the addition of benzyl isocyanate on the lactam nitrogen demonstrate activity against lipo-oliogosaccharide-containing bacteria, specifically Mycobacterium tuberculosis (Mtb). The focus of my research is to create a library of derivatives of these lactams with methoxy groups attached at various positions of the aromatic ring at C4 in-order to evaluate their activity against the aforementioned bacteria. SAR of these ether-containing-lactams against Mtb will be discussed.