The rise of antibiotic-resistant and non-tuberculous mycobacterial infections has placed ever-increasing importance on discovering new antibiotics to treat these diseases. Recently, a new penem, , was discovered to have strong antimicrobial activity against and . Here, a penem library of C2 side-chain variants was synthesized, and their antimicrobial activities were evaluated against HRv and ATCC 19977. Several new penems with antimicrobial activity stronger than the standard-of-care carbapenem antibiotics were identified with some candidates improving on the activity of the lead compound, . Moreover, many candidates showed little or no increase in the minimum inhibitory concentration in the presence of serum compared to the highly protein-bound . The penems with the strongest activity identified in this study were then biochemically characterized by reaction with the representative l,d-transpeptidase Ldt and the representative penicillin-binding protein d,d-carboxypeptidase DacB2.
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| http://dx.doi.org/10.1021/acsinfecdis.2c00229 | DOI Listing |
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