Dhiman, Pulkit and Das, Satyajeet and Pathania, Vikas and Rawat, Suraj and Nandanwar, Hemraj S and Thakur, Krishan G and Chaudhari, Vinod D (2025) Discovery of conformationally constrained dihydro Benzo-indole derivatives as metallo-β-lactamase inhibitors to tackle multidrug-resistant bacterial infections. J. Med. Chem., 68 (7). pp. 7062-7081.
Full text not available from this repository.Abstract
The discovery of metallo-β-lactamase (MBL) inhibitors is crucial in the fight against bacterial infections following the emergence and rapid spread of New Delhi metallo-β-lactamase-1 (NDM-1), as well as clinically relevant Verona integrin-encoded metallo-β-lactamase (VIM), and Imipenemase (IMP). The situation is alarming as there are insufficient antibiotics in the pipeline to combat critical multidrug-resistant infections. Here, we report the discovery of novel dihydrobenzo-indole (dBI) derivatives as a new class of potent metallo-β-lactamase inhibitors (MBLIs) by applying scaffold hopping, conformation constrained, and substituent-decorating strategies. Among them, compound 17u exhibited the best inhibitory activity against MBL with acceptable physicochemical and ADME properties. 17u exhibited remarkable enhancement of carbapenems' effectiveness against a range of MBL-producing clinical strains. This efficacy extended to in vivo settings when combined with the imipenem antibiotic, significantly reducing the bacterial load in a thigh infection model. Consequently, it qualifies as a prime candidate for further development as an MBLI.
| Item Type: | Article |
|---|---|
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 02 Feb 2026 07:15 |
| Last Modified: | 02 Feb 2026 07:15 |
| URI: | http://crdd.osdd.net/open/id/eprint/3218 |
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