Integrated experimental and computational evaluation of Anagallis foemina derived terpenoids against carbapenem resistant Acinetobacter baumannii

对金鸡菊(Anagallis foemina)来源的萜类化合物抗碳青霉烯类耐药鲍曼不动杆菌的活性进行实验和计算综合评价

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Abstract

As carbapenem resistance in Acinetobacter baumannii continues to rise worldwide, > 74% of clinical isolates are now resistant to carbapenemases. This pathogen has become a critical WHO priority and is associated with approximately 57,000 deaths per year; thus, the need for new antimicrobial agents is urgent. Here, we demonstrate that the ethanolic extract of Anagallis foemina Mill. has shown robust activity against MDR A. baumannii isolates from tertiary care hospitals. Gas chromatography-mass spectrometry (GC–MS) identified 16 bioactive compounds. Agar well diffusion assays showed an inhibition zone of 20.16 ± 0.29 mm at 15 mg/mL, exceeding that of imipenem (8 mm). The minimum inhibitory concentration (MIC) of 1.25 mg/mL, coupled with a minimum bactericidal concentration (MBC) of 2.5 mg/mL (MBC/MIC ratio = 2.0), indicated potent bactericidal activity. Sub-MIC concentrations inhibited biofilm formation by > 90%. Molecular docking showed moderate predicted binding between α-Terpinen-7-al (DockingScore: −5.4 kcal/mol) and γ-Terpinen-7-al (−5.3 kcal/mol) to OXA-24 β-lactamase. The complicated stability was verified for 100 ns production phases. Molecular dynamics simulations were carried out to confirm the stability of the complex and protein-ligand root mean square deviations (RMSD) of < 2.5 Å were obtained. Computational ADMET analysis revealed favorable drug-like properties, gastrointestinal absorption, and no toxicity risk. These findings identify A. foemina derived terpenoids as exploratory natural product leads warranting further investigation through isolated compound bioassays, enzyme kinetics, and cellular studies to validate predicted binding modes and antimicrobial potential against MDR A. baumannii. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-45012-3.

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