Pharmacological evaluation of disulfiram analogs as antimicrobial agents and their application as inhibitors of fosB-mediated fosfomycin resistance.

Disulfide analogs of the alcohol sobriety medication disulfiram (Antabuse®) were evaluated for antimicrobial activity. Structure-activity relationship analyses of MIC data obtained for methicillin-resistant Staphylococcus aureus (MRSA) and other pathogenic organisms revealed correlations between the lipophilicity and bulkiness of the substituents. Analogs conferring optimal anti-MRSA activity contained S-octyl disulfides and either N,N-dimethyl- or N-pyrrolidine dithiocarbamate substituents.

Moving towards fast characterization of polymorphic drugs by solid-state NMR spectroscopy.

Solid-state nuclear magnetic resonance (SS-NMR) spectroscopy has become a common technique to study polymorphism in pharmaceutical solids at high-resolution. However, high-throughput application of high resolution SS-NMR spectroscopy is severely limited by the long H spin-lattice relaxation (T) that is common to solid phase compounds. Here, we demonstrate the use of paramagnetic relaxation reagents such as chromium (III) acetylacetonate (Cr(acac)) and nickel (II) acetylacetonate (Ni(acac)) for fast data acquisition by significantly reducing the T value for carbamazepine Forms I, II, III, and dihydrate, cimetidine Forms A and B, nabumetone Form I, and acetaminophen Form I polymorphs.