Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens
Abstract
:1. Introduction
2. Staphylococcus aureus
Drug | Type | Mechanism of Action | Reference |
---|---|---|---|
Artemisinin | Antimalarial | Generates ROS and DNA damage | [35] |
Auranofin | Anti-inflammatory | Inhibits thioredoxin reductase | [37] |
BPH-652 | Cholesterol-lowering | Binds dehydrosqualene synthase (CrtM) | [34] |
Celecoxib | Anti-inflammatory | Inhibits multidrug efflux pumps | [29] |
Chlorpromazine | Antipsychotic | Accumulates in lysosomes, triggering antimicrobial activity | [22] |
Clomiphene | Fertility | Antagonizes wall teichoic acid | [25] |
Crizotinib | Antitumoral | ATP production | [5,28] |
Dasatinib | Antitumoral | Tyrosine kinase inhibitor | [15] |
Diflunisal | Anti-inflammatory | Inhibits the Agr system | [30] |
Dorsomorphin | AMPK inhibitor | Reduces autophagy and intracellular survival | [43] |
Ebselen | Anti-inflammatory | Inhibits thioredoxin reductase and thioredoxin | [26] |
Floxuridine | Antitumoral | Inhibits riboside phosphorylase | [32] |
Ibrutinib | Antitumoral | Controls the MEK/ERK/c-JUN signaling pathway | [15] |
Phenothiazine | Antipsychotic | Antagonism of dopamine D2 receptors | [11,13] |
Raloxifene | Estrogen receptor agonist | Induces autophagy and inhibits neutrophil cell death | [41] |
Selamectin | Anthelmintic | Shows high activity against S. aureus and M. tuberculosis | [28,41] |
Streptozotocin | Antitumoral | DNA synthesis inhibitor | [28,32] |
Thapsigargin | Ca2+ endoplasmic pump inhibitor | Increases host cell viability and reduces intracellular survival | [16,32] |
Thioridazine | Antipsychotic | Accumulates in macrophages, triggering antimicrobial activity | [16,22,23] |
3. Mycobacterium tuberculosis
Drug | Type | Mechanism of Action | Reference |
---|---|---|---|
Artemisinin | Antimalarial | Generates ROS and DNA damage | [74] |
Artesunate | Antimalarial | Unknown | [74] |
Atorvastatin | Statin | Enhances macrophage bactericidal effects | [50] |
Auranofin | Anti-inflammatory | Inhibits thioredoxin reductase | [37] |
Bazedoxifene | Estrogen receptor modulator | Reduces intracellular growth | [59] |
Bevacizumab | Antitumoral | Neutralizes VEGF | [65] |
Biapenem | Antimicrobial | Targets cell wall synthesis | [72] |
Chlorpromazine | Antipsychotic | NADH dehydrogenase type II inhibitor | [76] |
Faropenem | Antimicrobial | Targets cell wall synthesis | [72] |
Fluspirilene | Antipsychotic | Elicits autophagy | [56] |
Fluvastatin | Statin | Targets intracellular activity | [68] |
Gatifloxacin | Antimicrobial | DNA gyrase | [76] |
Ibuprofen | Anti-inflammatory | Reduces inflammatory response | [53] |
Ibrutinib | Antitumoral | Inhibits the BTK/Akt/mTOR pathway, triggering autophagy | [39] |
Imatinib | Antitumoral | Inhibits tyrosine kinases | [57] |
Imidazopyridine amides (Q203) | Antimicrobial | Cytochrome bc1 complex | [61] |
Ivermectin | Anthelmintic | Inhibits intracellular growth | [69] |
Metformin | Antidiabetic | Activates energy-sensing kinase and reduces inflammation | [63] |
Moxidectin | Anthelmintic | Unknown mechanism of action | [55] |
Nitroimidazofuran (PA-824) | Antimicrobial | Bacterial nitroreduction | [49] |
Nitazoxanide | Anthelmintic | Modulates host immune responses | [70] |
Phenothiazine | Antipsychotic | NADH inhibitor | [57,62] |
Pimozide | Antipsychotic | Affects ROS generation and inhibits STAT5 | [56] |
Saquinavir | Antiviral | Restores cathepsin protease activity | [48] |
Selamectin | Anthelmintic | Unknown mechanism of action | [55] |
Simvastatin | Statin | Reduces cholesterol uptake, showing synergy with antimicrobials | [51] |
Sulfadiazine | Antimicrobial | Inhibits folic acid synthesis | [66] |
Tamoxifen | Antitumoral | Induces autophagy | [55] |
Tebipenem | Antimicrobial | Targets cell wall synthesis | [72] |
Terlipressin | Vasoactive | Targets EmbC for cell wall synthesis | [67] |
Verapamil | Cardiovascular | Inhibits bacterial efflux pump | [39] |
Vitamin D | Vitamin | Activates TLR and induces autophagy | [54] |
4. Listeria monocytogenes
5. Salmonella enterica Serovar Typhimurium
Drug | Type | Mechanism of Action | Reference |
---|---|---|---|
Amoxapine | Antidepressant | Increase the levels of norepinephrine and serotonin | [74] |
Amenamevir | Antiviral | Inhibits helicase-primase complex | [75] |
Azacitidine | Antitumoral | Disrupts cytoplasmic membrane potential | [84] |
Bromperidol | Antipsychotic | Dopamine D2 receptor antagonist | [70] |
Carmofur | Antitumoral | Inhibitor dihydropyrimidine dehydrogenase | [84] |
Ciclopirox | Antifungal | Inhibits iron-dependent enzymes | [70] |
Diclofenac sodium | Anti-inflammatory | Inhibits prostaglandin G/H synthase | [74] |
Doxapram | Respiratory stimulant | Stimulates respiratory chemoreceptors | [74] |
Doxifluridine | Antitumoral | Inhibits thymidylate synthase | [70] |
Duvelisib | Antitumoral | Inhibits δ and γ isoforms PI3K | [75] |
Ethopropazine | Anticholinergic | Blocks muscarinic acetylcholine receptors | [70] |
Fluorouracil | Antitumoral | Disrupts cytoplasmic membrane potential | [84] |
Lifitegrast | Anti-inflammatory | Integrin agonist | [75] |
Loperamide | Antidiarrheal | Promotes autophagy | [89] |
Lovastatin | Anti-cholesterol | Inhibits HMG-CoA reductase | [72] |
Metergoline | Antipsychotic | Serotonin receptor antagonist | [70] |
Nilotinib | Antitumoral | Inhibits tyrosine kinase | [75] |
Trifluoperazine | Antipsychotic | Accumulates in macrophages, targets autophagy pathway | [88] |
6. Other Intracellular Pathogens
Drug | Type | Mechanism of Action | Pathogen | Reference |
---|---|---|---|---|
Capsaicin | Herbal compound | Induces autophagy | S. flexneri | [91] |
Diclofenac sodium | Anti-inflammatory | Inhibits prostaglandin G/H synthase | Shigella sp. | [87] |
Doxapram | Respiratory | Blocks intracellular colonization | Y. pestis | [88] |
Simvastatin | Statin | HMG-CoA inhibitor | C. pneumoniae | [94] |
Trifluoperazine | Antipsychotic | Accumulates in macrophages, targets autophagy pathway | C. pneumoniae, C. difficile, Y. pestis | [88] |
7. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Drug | Type | Mechanism of Action | Reference |
---|---|---|---|
Bepridil | Antitumoral | Inhibits calcium channel inhibitor | [67] |
Griseofulvin | Antifungal | Disruptor of microtubules | [69] |
Pimozide | Antipsychotic | Dopamine D2 receptor antagonist | [68] |
Thioridazine | Antipsychotic | Dopamine D2 receptor antagonist | [67] |
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Lorente-Torres, B.; Llano-Verdeja, J.; Castañera, P.; Ferrero, H.Á.; Fernández-Martínez, S.; Javadimarand, F.; Mateos, L.M.; Letek, M.; Mourenza, Á. Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens. Antibiotics 2024, 13, 834. https://doi.org/10.3390/antibiotics13090834
Lorente-Torres B, Llano-Verdeja J, Castañera P, Ferrero HÁ, Fernández-Martínez S, Javadimarand F, Mateos LM, Letek M, Mourenza Á. Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens. Antibiotics. 2024; 13(9):834. https://doi.org/10.3390/antibiotics13090834
Chicago/Turabian StyleLorente-Torres, Blanca, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek, and Álvaro Mourenza. 2024. "Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens" Antibiotics 13, no. 9: 834. https://doi.org/10.3390/antibiotics13090834