Synthesis and biological evaluation of Aspergillomarasmine A derivatives as novel NDM-1 inhibitor to overcome antibiotics resistance. Issue 19 (1st October 2017)

• Record Type: Journal Article
• Authors: Zhang, Jian; Wang, Sanshan; Wei, Qi; Guo, Qianqian; Bai, Yingjie; Yang, Shaoqiang; Song, Fuhang; Zhang, Lixin; Lei, Xiaoguang
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 19(2017)
• Page Start: 5133
• Page End: 5141
• Publication Date: 2017-10-01
• Subjects: Aspergillomarasmine A -- Antibiotic resistance -- Metallo-β-lactamases -- NDM-1 -- Antibiotics; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.07.025
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The β-lactam antibiotic resistance of Gram-negative bacteria has shown to be a critical global health problem. One of the primary reasons for the drug resistance is the existence of β-lactamases especially metallo-β-lactamases such as New Delhi metallo-β-lactamase (NDM-1) and Verona Integron-encoded metallo-β-lactamase (VIM-2). The fungal natural product Aspergillomarasmine A (AMA) has proven to be a promising inhibitor of NDM-1 and VIM-2 both in vitro and in vivo . Seven new analogues of AMA were synthesized by utilizing different strategies. The biological evaluation of these analogues was performed to study the structure-activity relationship of AMA both in vitro and in vivo . Remarkably, the lead compound 4 showed synergistic effect in combination with Meropenem to overcome the antibiotic resistance of the Gram-negative bacteria such as K. pneumoniae ( BAA-2146 ) expressing NDM-1.