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Abstract <p>The present study is focused on the design and synthesis of a series of acyl hydrazide derivatives based on pyrrolo[1,2-<i>c</i>]oxazin. Among which, four compounds with electron-donating groups substituted in their structures demonstrated notable antibacterial activity, particularly against Gram-positive bacteria and moderate antibacterial efficacy against <i>E. coli</i>. Further evaluation against MRSA revealed that compound bearing isopropyl substitution on the phenyl ring also possessed potent antibacterial activity. Investigations into resistance development against MRSA indicated that the MICs of this compound and norfloxacin exhibited a similar pattern of change. Subsequent synergistic antibacterial assays showed that these compounds could enhance the susceptibility of MRSA and <i>B. subtilis</i> 168 to kanamycin and chloramphenicol. The cytotoxicity of the derivatives was also assessed, revealing no significant impact on cell viability in HEK-293 and HK-2 cells at their respective MICs. The drug-likeness properties of these synthesized compounds were further evaluated in silico, demonstrating good to moderate oral bioavailability and moderate plasma protein binding rates. Mechanistic studies indicated that this type of compounds could disrupt cell membrane integrity and induce intracellular potassium ion outflow, ultimately leading to cell death. These findings suggest that acyl hydrazide derivatives based on pyrrolo[1,2-<i>c</i>]oxazin hold promise as potential leads for the development of antibacterial agents targeting antibiotic-resistant superbugs.</p>

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Synthesis and Biological Evaluation of Novel Acyl Hydrazide Derivatives Based on Heterocyclic Core as Antibacterial Agents

  • 期刊论文

  • 发表日期：

    2025年7月1日

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  • Y. Li,
  • T. Ye,
  • Q. Yuan,
  • Z. Zhou,
  • H. Hu,
  • Y. Xin

摘要

Abstract

The present study is focused on the design and synthesis of a series of acyl hydrazide derivatives based on pyrrolo[1,2-c]oxazin. Among which, four compounds with electron-donating groups substituted in their structures demonstrated notable antibacterial activity, particularly against Gram-positive bacteria and moderate antibacterial efficacy against E. coli. Further evaluation against MRSA revealed that compound bearing isopropyl substitution on the phenyl ring also possessed potent antibacterial activity. Investigations into resistance development against MRSA indicated that the MICs of this compound and norfloxacin exhibited a similar pattern of change. Subsequent synergistic antibacterial assays showed that these compounds could enhance the susceptibility of MRSA and B. subtilis 168 to kanamycin and chloramphenicol. The cytotoxicity of the derivatives was also assessed, revealing no significant impact on cell viability in HEK-293 and HK-2 cells at their respective MICs. The drug-likeness properties of these synthesized compounds were further evaluated in silico, demonstrating good to moderate oral bioavailability and moderate plasma protein binding rates. Mechanistic studies indicated that this type of compounds could disrupt cell membrane integrity and induce intracellular potassium ion outflow, ultimately leading to cell death. These findings suggest that acyl hydrazide derivatives based on pyrrolo[1,2-c]oxazin hold promise as potential leads for the development of antibacterial agents targeting antibiotic-resistant superbugs.