Drug Repurposing: New Ways for Known Medicines
DOI:
https://doi.org/10.18633/biotecnia.v27.2591Keywords:
Repurposing, non-steroidal anti-inflammatory, sildenafil, omeprazole, bioinformaticsAbstract
Drug repositioning is a strategy that leverages approved medications to treat diseases for which they were not originally designed. This approach reduces the time and costs associated with developing new drugs, facilitating the discovery of new therapeutic options. This review aims to explore the methodologies used, the current challenges, and the potential impact of this approach in medicine. A search was conducted in the PubMed and ScienceDirect databases using keywords related to drug repositioning, combining terms such as “repurposing” with different types of medications. The most recent information was prioritized, specifically for the last 15 years (with 2010 used as a threshold), and articles deemed irrelevant or outdated were excluded. Successful repositioning cases are highlighted, such as ibuprofen, a Non-Steroidal Anti-Inflammatory Drug (NSAID), which may offer benefits in neurodegenerative diseases. Acetylsalicylic acid, initially designed for hypertension and angina, has presented activity against cancer and Alzheimer’s disease. Omeprazole, used for acid-related secretory disorders, has shown antiparasitic activity. These examples emphasize how approved drugs, with established safety profiles, can have new uses. Drug repositioning, supported by bioinformatics tools, represents a promising avenue for treating neglected diseases and improving existing therapies through drug combinations that optimize efficacy and reduce side effects.
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References
Amano, Y., Namatame, I., Tateishi, Y., Honboh, K., Tanabe, E., Niimi, T., & Sakashita, H. (2015). Structural insights into the novel inhibition mechanism of Trypanosoma cruzi spermidine synthase. Acta Crystallographica. Section D, Biological Crystallography, 71(Pt 9), 1879–1889.
Borba-Santos, L. P., Nucci, M., Ferreira-Pereira, A., & Rozental, S. (2021). Anti-Sporothrix activity of ibuprofen combined with antifungal. Brazilian Journal of Microbiology, 52(1), 101.
Chan, A. T., Giovannucci, E. L., Meyerhardt, J. A., Schernhammer, E. S., Curhan, G. C., & Fuchs, C. S. (2005). Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA, 294(8), 914–923.
Chan, A. T., Giovannucci, E. L., Meyerhardt, J. A., Schernhammer, E. S., Wu, K., & Fuchs, C. S. (2008). Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology, 134(1), 21–28.
Chan, A. T., Ogino, S., & Fuchs, C. S. (2007). Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. The New England Journal of Medicine, 356(21), 2131–2142.
Chen, L., Liu, Y., Becher, A., DIepold, K., Schmid, E., Fehn, A., Brunner, C., Rouhi, A., Chiosis, G., Cronauer, M., Seufferlein, T., & Azoitei, N. (2020). Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2. Carcinogenesis, 41(10), 1421–1431.
Cofer, L. B., Barrett, T. J., & Berger, J. S. (2022). Aspirin for the Primary Prevention of Cardio-vascular Disease: Time for a Platelet-Guided Approach. Arteriosclerosis, Thrombosis, and Vascular Biology, 42(10), 1207–1216.
Das, A., Durrant, D., Mitchell, C., Mayton, E., Hoke, N. N., Salloum, F. N., Park, M. A., Qureshi, I., Lee, R., Dent, P., & Kukreja, R. C. (2010). Sildenafil increases chemotherapeutic efficacy of dox-orubicin in prostate cancer and ameliorates cardiac dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 107(42), 18202–18207.
Fijałkowski, Ł., Skubiszewska, M., Grześk, G., Koech, F. K., & Nowaczyk, A. (2022). Acetylsali-cylic Acid–Primus Inter Pares in Pharmacology. Molecules 2022, Vol. 27, Page 8412, 27(23), 8412.
García-Torres, I., De La Mora-De La Mora, I., Marcial-Quino, J., Gómez-Manzo, S., Vanoye-Carlo, A., Navarrete-Vázquez, G., Colín-Lozano, B., Gutiérrez-Castrellón, P., Sierra-Palacios, E., Ló-pez-Velázquez, G., & Enríquez-Flores, S. (2016). Proton pump inhibitors drastically modify tri-osephosphate isomerase from Giardia lamblia at functional and structural levels, providing molecular leads in the design of new antigiardiasic drugs. Biochimica et Biophysica Acta, 1860(1 Pt A), 97–107.
Ghofrani, H. A., Osterloh, I. H., & Grimminger, F. (2006). Sildenafil: from angina to erectile dys-function to pulmonary hypertension and beyond. Nature Reviews. Drug Discovery, 5(8), 689.
Gohel, D., Zhang, P., Gupta, A. K., Li, Y., Chiang, C. W., Li, L., Hou, Y., Pieper, A. A., Cummings, J., & Cheng, F. (2024). Sildenafil as a Candidate Drug for Alzheimer’s Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons. Journal of Alzheimer’s Disease : JAD, 98(2), 643–657.
Guo, C. G., Ma, W., Drew, D. A., Cao, Y., Nguyen, L. H., Joshi, A. D., Ng, K., Ogino, S., Mey-erhardt, J. A., Song, M., Leung, W. K., Giovannucci, E. L., & Chan, A. T. (2021). Aspirin Use and Risk of Colorectal Cancer Among Older Adults. JAMA Oncology, 7(3), 1.
Hersh, E. V., Hammond, B. F., & Fleury, A. A. P. (1991). Antimicrobial activity of flurbiprofen and ibuprofen in vitro against six common periodontal pathogens. The Journal of Clinical Dentistry, 3(1), 1–5.
Juárez-Saldivar, A., Schroeder, M., Salentin, S., Joachim Haupt, V., Saavedra, E., Vázquez, C., Reyes-Espinosa, F., Herrera-Mayorga, V., Villalobos-Rocha, J. C., García-Pérez, C. A., Campillo, N. E., & Rivera, G. (2020). Computational Drug Repositioning for Chagas Disease Using Pro-tein-Ligand Interaction Profiling. International Journal of Molecular Sciences 2020, Vol. 21, Page 4270, 21(12), 4270.
Kaur, D., Choudhury, C., Yadav, R., Kumari, L., & Bhatia, A. (2024). Aspirin as a potential drug repurposing candidate targeting estrogen receptor alpha in breast cancer: a molecular dynamics and in-vitro study. Journal of Biomolecular Structure and Dynamics.
Konstan, M. W., Byard, P. J., Hoppel, C. L., & Davis, P. B. (1995). Effect of High-Dose Ibuprofen in Patients with Cystic Fibrosis. New England Journal of Medicine, 332(13), 848–854.
Lands, L. C., & Dauletbaev, N. (2010). High-Dose Ibuprofen in Cystic Fibrosis. Pharmaceuticals, 3(7), 2213.
Lands, L. C., & Stanojevic, S. (2019). Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis. Cochrane Database of Systematic Reviews, 2019(9).
Patrono, C., & Rocca, B. (2021). Aspirin at 120: Retiring, recombining, or repurposing? Research and Practice in Thrombosis and Haemostasis, 5(4).
Pérez-Villanueva, J., Romo-Mancillas, A., Hernández-Campos, A., Yépez-Mulia, L., Hernán-dez-Luis, F., & Castillo, R. (2011). Antiprotozoal activity of proton-pump inhibitors. Bioorganic & Medicinal Chemistry Letters, 21(24), 7351–7354.
Pina-Vaz, C., Sansonetty, F., Rodrigues, A. G., Martinez-De-Oliveira, J., Fonseca, A. F., & Mardh, P. A. (2000). Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species. Journal of Medical Microbiology, 49(9), 831–840.
Planer, J. D., Hulverson, M. A., Arif, J. A., Ranade, R. M., Don, R., & Buckner, F. S. (2014). Synergy Testing of FDA-Approved Drugs Identifies Potent Drug Combinations against Trypano-soma cruzi. PLOS Neglected Tropical Diseases, 8(7), e2977.
Reigada, C., Valera-Vera, E. A., Sayé, M., Errasti, A. E., Avila, C. C., Miranda, M. R., & Pereira, C. A. (2017). Trypanocidal Effect of Isotretinoin through the Inhibition of Polyamine and Amino Acid Transporters in Trypanosoma cruzi. PLOS Neglected Tropical Diseases, 11(3), e0005472.
Reyes-Vivas, H., De La Mora-De La Mora, I., Castillo-Villanueva, A., Yépez-Mulia, L., Hernán-dez-Alcántara, G., Figueroa-Salazar, R., García-Torres, I., Gómez-Manzo, S., Méndez, S. T., Va-noye-Carlo, A., Marcial-Quino, J., Torres-Arroyo, A., Oria-Hernández, J., Gutiérrez-Castrellón, P., Enríquez-Flores, S., & López-Velázquez, G. (2014). Giardial Triosephosphate Isomerase as Possible Target of the Cytotoxic Effect of Omeprazole in Giardia lamblia. Antimicrobial Agents and Chemotherapy, 58(12), 7072.
Rial, M. S., Reigada, C., Prado, N., Bua, J., Esteva, M., Pereira, C. A., & Fichera, L. E. (2023). Effectiveness of the repurposed drug isotretinoin in an experimental murine model of Chagas dis-ease. Acta Tropica, 242.
Sanyal, A. K., Roy, D., Chowdhury, B., & Banerjee, A. B. (1993). Ibuprofen, a unique anti‐inflammatory compound with antifungal activity against dermatophytes. Letters in Applied Micro-biology, 17(3), 109–111.
Shah, P. N., Marshall-Batty, K. R., Smolen, J. A., Tagaev, J. A., Chen, Q., Rodesney, C. A., Le, H. H., Gordon, V. D., Greenberg, D. E., & Cannon, C. L. (2018). Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens. Antimicrobial Agents and Chemo-therapy, 62(3).
Sobhani, K., Li, J., & Cortes, M. (2023). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). First Aid Perioperative Ultrasound: Acute Pain Manual for Surgical Procedures, 127–138.https://doi.org/10.1007/978-3-031-21291-8_8
Tantry, U.S., Schror, K., Navarese, E.P., Jeong, Y.H., Kubica, J., Bliden, K.P. and Gurbel, P.A. 2021. Aspirin as an adjunctive pharmacologic therapy option for COVID-19: Anti inflammatory, antithrombotic, and antiviral effects all in one agent. Journal of Experimental Pharmacology, 13, 957. https://doi.org/10.2147/JEP.S330776
Ter Horst, S., Conceição-Neto, N., Neyts, J. and Rocha-Pereira, J. 2019. Structural and functional similarities in bunyaviruses: Perspectives for pan-bunya antivirals. Reviews in Medical Virology, 29(3), e2039. https://doi.org/10.1002/RMV.2039
Vázquez, C., Encalada, R., Jiménez-Galicia, I., Gómez-Escobedo, R., Rivera, G., Nogueda-Torres, B. and Saavedra, E. 2024. Repurposing the antidiabetic drugs glyburide, gliquidone, and glipizide in combination with benznidazole for Trypanosoma cruzi infection. Pharmaceuticals (Basel, Switzerland), 18(1). https://doi.org/10.3390/PH18010021
Veljkovic, V., Glisic, S., Muller, C.P., Scotch, M., Branch, D.R., Perovic, V.R., Sencanski, M., Veljkovic, N. and Colombatti, A. 2015. In silico analysis suggests interaction between Ebola virus and the extracellular matrix. Frontiers in Microbiology, 6(FEB). https://doi.org/10.3389/FMICB.2015.00135
Veljkovic, V., Goeijenbier, M., Glisic, S., Veljkovic, N., Perovic, V.R., Sencanski, M., Branch, D.R. and Paessler, S. 2015. In silico analysis suggests repurposing of ibuprofen for prevention and treatment of EBOLA virus disease. F1000Research, 4, 104. https://doi.org/10.12688/F1000RESEARCH.6436.1
Wong, M.W., Yi, C.H., Liu, T.T., Lei, W.Y., Hung, J.S., Liu, C.Z. and Chen, C.L. 2021. Effects of phosphodiesterase-5 inhibitor sildenafil on esophageal secondary peristalsis: Studies with high-resolution manometry. Journal of Gastroenterology and Hepatology, 36(2), 430–435. https://doi.org/10.1111/JGH.15170
Xia, Y., Sun, M., Huang, H. and Jin, W.L. 2024. Drug repurposing for cancer therapy. Signal Transduction and Targeted Therapy, 9(1). https://doi.org/10.1038/S41392-024-01808-1
Zhen, J., Zhang, C., Huang, T., Xie, L., Yan, Y., Yan, S., Zhang, J., Huang, H. and Xie, J. 2024. Drug repurposing: An antidiabetic drug Ipragliflozin as Mycobacterium tuberculosis sirtuin-like protein inhibitor that synergizes with anti-tuberculosis drug isoniazid. International Journal of Biological Macromolecules, 282, 137003. https://doi.org/10.1016/J.IJBIOMAC.2024.137003
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