Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.

Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.
Bioorg Med Chem. 2020 Dec 03;29:115902
Authors: Ma G, Wang S, Wu K, Zhang W, Ahmad A, Hao Q, Lei X, Zhang H
Abstract
β-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-β-lactamase 1 (NDM-1) is able to hydrolyze nearly all β-lactam antibiotics and even clinically used serine-β-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed. Here we report a series of structure-guided design of D-captopril derivatives that can inhibit the activity of NDM-1 in vitro and at cellular levels. Structural comparison indicates the mechanisms of inhibition enhancement and provides insights for further inhibitor optimization.
PMID: 33302045 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - December 3, 2020 Category: Chemistry Authors: Ma G, Wang S, Wu K, Zhang W, Ahmad A, Hao Q, Lei X, Zhang H Tags: Bioorg Med Chem Source Type: research