2. Academic Validation
  3. Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic β-lactam DPI-2016

Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic β-lactam DPI-2016

  • Bioorg Med Chem Lett. 2024 Jan 8:129615. doi: 10.1016/j.bmcl.2024.129615.
Lijuan Zhai 1,  Jian Sun 1,  Jingwen Ji 2,  Lili He 1,  Pengjuan Zhou 1,  Dong Tang 1,  Jinbo Ji 1,  Haikang Yang 1,  Zafar Iqbal 3,  Zhixiang Yang 4
Affiliations

Affiliations

  • 1 Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, PR China.
  • 2 Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, PR China. Electronic address: [email protected].
  • 3 Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, PR China. Electronic address: [email protected].
  • 4 Ningxia Centre of Organic Synthesis and Engineering Technology, Ningxia Academy of Agriculture and Forestry Sciences, No. 590, Huanghe East Road, Jinfeng District, Yinchuan, Ningxia 750002, PR China. Electronic address: [email protected].
PMID: 38199331 DOI: 10.1016/j.bmcl.2024.129615
Abstract

Monocyclic β-lactams are stable to a number of β-lactamases and are the focus of researchers for the development of Antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to find the maximum final yields aimed at large-scale synthesis. In addition, the results of the pharmacological studies were determined with reference to aztreonam. It has been found that the compound DPI-2016 showed comparable or slightly improved ADMET as well as pharmacokinetic parameters to aztreonam. It is estimated that the compound could be a potential lead for further clinical evaluation.

Keywords

Antibacterial; Aztreonam; Monobactam; β-lactams.

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