Recently, aryl-ureidothiophene carboxylates were shown to inhibit the RNA polymerase and reduce the growth of Gram positive bacteria. We now aimed to extend the efficacy spectrum and address presumed permeation deficiencies of these agents by applying different prodrug-approaches. Chemical syntheses yielded 12 prodrugs of three different categories featuring neutral, cationic and Fe-III -coordinating properties. Their promising characteristics regarding stabilities, enzyme-activation and iron coordination performance encouraged their study in growth inhibition assays of different Gram positive and Gram negative bacterial strains. These studies pointed to a positively charged, choline-like motif being beneficial for these compounds especially for Gram-negative bacterial cell growth inhibition.