Guixing Ma, Sanshan Wang , Kebin Wu, Weizhe Zhang, Ashfaq Ahmad, Quan Hao *,Xiaoguang Lei *, Hongmin Zhang *
Bioorganic and Medicinal Chemistry 29.(2021) .115902
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.
Guixing Ma, Sanshan Wang , Kebin Wu, Weizhe Zhang, Ashfaq Ahmad, Quan Hao *,Xiaoguang Lei *, Hongmin Zhang *
Bioorganic and Medicinal Chemistry 29.(2021) .115902
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.