Novel antibacterial class: a series of tetracyclic derivatives.
Hinman MM, Rosenberg TA, Balli D, Black-Schaefer C, Chovan LE, Kalvin D, Merta PJ, Nilius AM, Pratt SD, Soni NB, Wagenaar FL, Weitzberg M, Wagner R, Beutel BA.
We describe the synthesis and antibacterial activity of a series of tetracyclic naphthyridones. The members of this series act primarily via inhibition of bacterial translation and belong to the class of novel ribosome inhibitors (NRIs). In this paper we explore the structure-activity relationships (SAR) of these compounds to measure their ability both to inhibit bacterial translation and also to inhibit the growth of bacterial cells in culture. The most active of these compounds inhibit Streptococcus pneumoniae translation at concentrations of <5 microM and have minimum inhibitory concentrations (MICs) of <8 microg/mL against clinically relevant strains of bacteria.