2. Academic Validation
  3. Quercetin as a promising HIS-C inhibitor and novel therapeutic against antibacterial drug-resistant Acinetobacter baumannii: in vitro and in silico insights

Quercetin as a promising HIS-C inhibitor and novel therapeutic against antibacterial drug-resistant Acinetobacter baumannii: in vitro and in silico insights

  • Naunyn Schmiedebergs Arch Pharmacol. 2025 Nov 20. doi: 10.1007/s00210-025-04749-w.
Mohammed Salleh M Ardawi 1,  Samar A Badreddine 2,  Muhammad Yasir 1 3 4,  Safaa A Turkistani 5,  Ahmed Afandi 6,  Abdulaziz A Kimawi 7,  Samah O Noor 8,  Adhari Alselmi 9 10,  Salma Mohammed Alsayed 3 8 11,  Mada S Alharthi 3 8 12,  Vivek Dhar Dwivedi 13 14,  Pradeep Sharma 15,  Esam I Azhar 16 17
Affiliations

Affiliations

  • 1 Department of Pathological Sciences, Fakeeh College for Medical Sciences, and Fakeeh Care Group, Jeddah, Saudi Arabia.
  • 2 Infection Control Department, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia.
  • 3 Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
  • 4 Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
  • 5 Medical Laboratory Sciences, Fakeeh College for Medical Sciences, and Fakeeh Care Group, Jeddah, Saudi Arabia.
  • 6 Department of Surgery, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.
  • 7 Department of Surgery, Dr. Soliman Fakeeh Hospital, Jeddah, Saudi Arabia.
  • 8 Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 9 Clinical Sciences Department-MBBS Program, Fakeeh College for Medical Sciences, 21461, Jeddah, Saudi Arabia.
  • 10 Dr. Soliman Fakeeh Medical Center, Jeddah, Saudi Arabia.
  • 11 Department of Emergency Medical Services, Faculty of Health Sciences-Al Qunfudah,, Umm Al-Qura University, Makkah, Saudi Arabia.
  • 12 Department of Medical Laboratory Science, College of Applied Medical Sciences, Shaqra University, 11961, Shaqra, Saudi Arabia.
  • 13 Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospitals, Saveetha University, Chennai, India.
  • 14 Bioinformatics Research Division, Quanta Calculus, Greater Noida, India.
  • 15 Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India. [email protected].
  • 16 Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, 21589, Jeddah, Saudi Arabia. [email protected].
  • 17 Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, 21589, Jeddah, Saudi Arabia. [email protected].
PMID: 41263994 DOI: 10.1007/s00210-025-04749-w
Abstract

Acinetobacter baumannii (A. baumannii), a common hospital-associated pathogen, is known for its rapid ability to develop Antibacterial drug resistance. The HIS-C enzyme in this pathogen is essential for histidine biosynthesis, making this a prominent drug target for antimicrobial therapy. This experimental investigation analyzes the inhibitory function of quercetin, a well-known Antibacterial flavonoid, on HIS-C enzyme through the in vitro and in silico approaches. The binding affinity between quercetin and HIS-C was further examined through in vitro assays. Further, the surface plasmon resonance (SPR) experiments confirmed the strong binding affinity, with a dissociation constant (KD) of 3.3 × 10-6 M. Antibacterial assays proved the inhibitory potential of quercetin against A. baumannii growth, with a minimum inhibitory concentration (MIC) of 15 µg/mL. In silico analyses were performed to support these experimental results by providing additional insights into the binding interactions. Altogether, these in vitro and in silico findings have significantly proven the potential of quercetin as an HIS-C inhibitor. Further in vivo studies, particularly on toxicity and pharmacokinetics, are essential before it can be considered for therapeutic application against A. baumannii infections.

Keywords

Acinetobacter baumannii; HIS-C enzyme; Quercetin.

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