Repurposing amlodipine, fluoxetine, and escitalopram as non-antibiotic adjuvants: in vitro enhancement of ciprofloxacin and fluconazole activity against multidrug-resistant bacterial and candida clinical isolates.
5 affiliations
- 1Department of Pharmacology, Faculty of Pharmacy, Sana'a University, Sana'a, Yemen.
- 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sana'a University, Sana'a, Yemen. [email protected].
- 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Sana'a University, Sana'a, Yemen.
- 4Department of Medicinal Chemistry, Faculty of Pharmacy, Sana'a University, Sana'a, Yemen.
- 5Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia. [email protected].
Abstract
Introduction
Multidrug-resistant (MDR) Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans threaten treatment success, particularly in resource-limited settings. Repurposing licensed, inexpensive non-antibiotic drugs may provide a strategy for enhancing the activity of established antimicrobial agents.Methods
Clinical isolates from Sana'a, Yemen, and American Type Culture Collection (ATCC) reference strains were tested in vitro with amlodipine, fluoxetine, and escitalopram, individually and in dual or triple combinations with ciprofloxacin or fluconazole. Antimicrobial activity was evaluated using agar-well diffusion, broth microdilution minimum inhibitory concentration (MIC), minimum bactericidal or fungicidal concentration (MBC/MFC), and checkerboard fractional inhibitory concentration index (FICI) assays. Molecular docking with AutoDock Vina was used to explore plausible interactions with MurB (PDB 1HSK), LasR (PDB 3IX3), and CYP51 (PDB 5V5Z). Normal mode analysis (NMA) with iMODS was performed for selected fluoxetine-LasR and fluoxetine-MurB complexes as a preliminary structural-dynamics assessment.Results
Fluoxetine produced inhibition zones of at least 27 mm across the tested organisms. Amlodipine produced larger zones against S. aureus and C. albicans than against P. aeruginosa, whereas escitalopram produced smaller zones overall. Checkerboard testing identified synergy (FICI ≤ 0.50) for selected combinations. Selected triple combinations reduced MIC values by 4- to 64-fold. The largest diffusion readouts were observed with ciprofloxacin + fluoxetine + amlodipine against S. aureus (101 mm), ciprofloxacin + fluoxetine + escitalopram against P. aeruginosa (88.5 mm), and ciprofloxacin + amlodipine + fluconazole against C. albicans (138.5 mm). Docking scores and NMA outputs provided hypothesis-generating structural context for the experimental findings.Conclusions
Antimicrobial enhancement was combination- and organism-dependent. Selected combinations showed checkerboard-defined synergy, whereas diffusion assays were interpreted as screening outcomes only. Docking and NMA findings were supportive and hypothesis-generating but did not establish target engagement or mechanism.
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BibTeX
@article{alkhawlani2026repurposing,
title = {{Repurposing amlodipine, fluoxetine, and escitalopram as non-antibiotic adjuvants: in vitro enhancement of ciprofloxacin and fluconazole activity against multidrug-resistant bacterial and candida clinical isolates.}},
author = {Mohammed A Alkhawlani and Wafa M Al-Madhagi and Mahmoud Mahyoob Alburyhi and Ali Gamal Al-Kaf and Maged Al-Najar},
journal = {BMC microbiology},
year = {2026},
month = jul,
doi = {10.1186/s12866-026-05443-4},
url = {https://europepmc.org/article/MED/42894131},
note = {CC BY},
}
RIS
TY - JOUR
TI - Repurposing amlodipine, fluoxetine, and escitalopram as non-antibiotic adjuvants: in vitro enhancement of ciprofloxacin and fluconazole activity against multidrug-resistant bacterial and candida clinical isolates.
AU - Mohammed A Alkhawlani
AU - Wafa M Al-Madhagi
AU - Mahmoud Mahyoob Alburyhi
AU - Ali Gamal Al-Kaf
AU - Maged Al-Najar
PY - 2026
DA - 2026/07/01
JO - BMC microbiology
DO - 10.1186/s12866-026-05443-4
UR - https://europepmc.org/article/MED/42894131
AB - Introduction Multidrug-resistant (MDR) Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans threaten treatment success, particularly in resource-limited settings. Repurposing licensed, inexpensive non-antibiotic drugs may provide a strategy for enhancing the activity of established antimicrobial agents.Methods Clinical isolates from Sana'a, Yemen, and American Type Culture Collection (ATCC) reference strains were tested in vitro with amlodipine, fluoxetine, and escitalopram, individually and in dual or triple combinations with ciprofloxacin or fluconazole. Antimicrobial activity was evaluated using agar-well diffusion, broth microdilution minimum inhibitory concentration (MIC), minimum bactericidal or fungicidal concentration (MBC/MFC), and checkerboard fractional inhibitory concentration index (FICI) assays. Molecular docking with AutoDock Vina was used to explore plausible interactions with MurB (PDB 1HSK), LasR (PDB 3IX3), and CYP51 (PDB 5V5Z). Normal mode analysis (NMA) with iMODS was performed for selected fluoxetine-LasR and fluoxetine-MurB complexes as a preliminary structural-dynamics assessment.Results Fluoxetine produced inhibition zones of at least 27 mm across the tested organisms. Amlodipine produced larger zones against S. aureus and C. albicans than against P. aeruginosa, whereas escitalopram produced smaller zones overall. Checkerboard testing identified synergy (FICI ≤ 0.50) for selected combinations. Selected triple combinations reduced MIC values by 4- to 64-fold. The largest diffusion readouts were observed with ciprofloxacin + fluoxetine + amlodipine against S. aureus (101 mm), ciprofloxacin + fluoxetine + escitalopram against P. aeruginosa (88.5 mm), and ciprofloxacin + amlodipine + fluconazole against C. albicans (138.5 mm). Docking scores and NMA outputs provided hypothesis-generating structural context for the experimental findings.Conclusions Antimicrobial enhancement was combination- and organism-dependent. Selected combinations showed checkerboard-defined synergy, whereas diffusion assays were interpreted as screening outcomes only. Docking and NMA findings were supportive and hypothesis-generating but did not establish target engagement or mechanism.
SN - 1471-2180
ER -