Evaluation of A22 Analogs as Gram-negative Antimicrobial Agents

Abstract S-(3,4-dichlorobenzyl) isothiourea (A22) and mecillinam are the only known antibacterial agents that act on the rod-shape maintenance mechanism of rod-like bacteria. This makes A22 an attractive lead compound for developing antibiotics with novel mechanism of action. In this study we expanded a limited structure activity relation (SAR) study previously reported and determined the effect of fused carbocyclic and heterocyclic analogs of A22 against three Gram-negative bacteria. Also, the efflux liabilities of the analogs generated here were examined in E. coli and P. aeruginosa.