2. Academic Validation
  3. Novel aminophosphoryl hybridization of natural berberine and heterocyclic azoles with large potential to combat global increasing bacterial resistance

Novel aminophosphoryl hybridization of natural berberine and heterocyclic azoles with large potential to combat global increasing bacterial resistance

  • Bioorg Chem. 2026 Jun 15:174:109725. doi: 10.1016/j.bioorg.2026.109725.
Yu Zhou 1,  Ying Yang 2,  Aisha Bibi 1,  Wei-Wei Gao 3,  Shao-Lin Zhang 4,  Cheng-He Zhou 5
Affiliations

Affiliations

  • 1 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
  • 2 School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.
  • 3 State Key Laboratory Base of Eco-chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address: gww501@qust.edu.cn.
  • 4 School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China. Electronic address: zhangsl@cqu.edu.cn.
  • 5 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: zhouch@swu.edu.cn.
PMID: 41797130 DOI: 10.1016/j.bioorg.2026.109725
Abstract

Unique aminophosphoryl hybridization of natural berberine with heterocyclic azoles was conducted to access novel Antibacterial agents with large potential to combat deadly Bacterial resistance. Some prepared berberine conjugates effectively inhibited the growth of tested bacteria, particularly, methyloxazolyl aminosulfonylphenyl conjugate I-10b showed stronger Antibacterial effects than berberine, norfloxacin and sulfanilamides (sulfamethoxazole, sulfadiazine, sulfacetamide and sulfathiazole). Moreover, compound I-10b exhibited potent activity against sulfamethoxazole-resistant bacteria. Conjugate I-10b exhibited low drug resistance, hemolysis, cytotoxicity and in vivo toxicity as well as rapid bactericidal properties, and effective transportation by human serum albumin. Highly active conjugate I-10b could trigger Reactive Oxygen Species accumulation, form I-10b-DNA supramolecular complex by intercalation to block DNA replication and inhibit Lactate Dehydrogenase to disturb metabolism, and further prompt Bacterial cell rupture to induce the leakage of intracellular content, ultimately causing Bacterial death. Moreover, conjugate I-10b displayed potent efficacy against S. aureus 25,923 in both G. Mellonella larval and murine wound Infection models. These results suggested the potential of the developed azolyl aminophosphoryl berberines as effective Antibacterial candidates.

Keywords

Aminophosphate; Antibacterial; Azole; Berberine; Multitargeting.

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