The dark side of drug repurposing. From clinical trial challenges to antimicrobial resistance: analysis based on three major fields


  • Iyad Y. Natsheh Department of Medical Applied Sciences, Zarqa University College, Al-Balqa Applied University, Salt - Jordan
  • Majd M. Alsaleh Department of Medical Applied Sciences, Zarqa University College, Al-Balqa Applied University, Salt - Jordan and Department of Biology, School of Science, University of Jordan, Amman - Jordan
  • Ahmad K. Alkhawaldeh Department of Medical Applied Sciences, Zarqa University College, Al-Balqa Applied University, Salt - Jordan
  • Duaa K. Albadawi Department of Medical Applied Sciences, Zarqa University College, Al-Balqa Applied University, Salt - Jordan
  • Maisa’ M. Darwish Department of Biology, School of Science, University of Jordan, Amman - Jordan and National Agricultural Research Center, Amman - Jordan
  • Mohammed Jamal A. Shammout Chemistry Department, Faculty of Science, Applied Science Private University, Amman - Jordan



Thalidomide, Levofloxacin, Minocycline, Doxycycline, Azithromycin, Hydroxychloroquine


Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields—cardiovascular, cancer, and diabetes—and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.


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Agnihotri Jaya, R Sunanda, Patil et al. “Drug repurposing: A futuristic approach in drug discovery”. Journal of pharmaceutical and biological sciences, vol. 11, no. 1, 66–69, 2023.

Hyeong-Min L, Yuna K. Drug repurposing is a new opportunity for developing drugs against neuropsychiatric disorders. Schizophr Res Treatment. 2016;2016:6378137. DOI:

Meera M, Sekar S, Mahatao R. A novel approach for drug discovery-drug repurposing. Natl J Physiol Pharm Pharmacol. 2022;12(5):546-551. DOI:

Iacopetta D. Special issue on “anticancer drugs activity and underlying mechanisms”. Appl Sci (Basel). 2021;11(17):8169. DOI:

Pardo-Yules B, Gallego-Durán R, Eslam M, et al. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept. Rev Esp Enferm Dig. 2011;103(12):619-625. PMID:22217345 DOI:

Jesus SM, Santana RS, Leite SN. The organization, weaknesses, and challenges of the control of thalidomide in Brazil: a review. PLoS Negl Trop Dis. 2020;14(8):e0008329. PMID:32760161 DOI:

Duarte D, Vale N. Antidepressant drug sertraline against human cancer cells. Biomolecules. 2022;12(10):1513. PMID:36291722 DOI:

Rehan M, Ahmed F, Howladar SM, et al. A computational approach identified andrographolide as a potential drug for suppressing Covid-19-induced cytokine storm. Front Immunol. 2021;12:648250. DOI:

Talib Jawad Kadhim, Omer Abd Alkareem Khalf. A review search of sildenafil uses in human and in the veterinary medicine. AIP Conf Proc. 2023;2475:100010. DOI:

Al Ibrahim AH, Ghallab KQ, Alhumaid FI, et al. A systematic review of sildenafil mortality through the years. Cureus. 2022;14(12):e32179. DOI:

Hussein MA, Salah El-Din MM, Saleh EM, et al. Sildenafil (VIAGRATM): a promising anticancer drug against certain human cancer cell lines. Asian J Chem. 2021;33(6):1420-1424. DOI:

Goldstein I, Burnett AL, Rosen RC, et al. The serendipitous story of sildenafil: an unexpected oral therapy for erectile dysfunction. Sex Med Rev. 2019;7(1):115-128. PMID:30301707 DOI:

Ala M, Jafari RM, Dehpour AR. Sildenafil beyond erectile dysfunction and pulmonary arterial hypertension: thinking about new indications. Fundam Clin Pharmacol. 2021;35(2):235-259,. DOI:

Mpoeo, A Baa, Ky. Hooe peaaee capx eapc (oop). apaoa pecpa eapcex cpec, 2023;12(1):182-190. DOI:

Krishnamurthy N, Grimshaw AA, Axson SA, Choe SH, Miller JE. Drug repurposing: a systematic review on root causes, barriers and facilitators. BMC Health Serv Res. 2022;22(1):1-17. PMID:34974828 DOI:

Trivedi J, Mohan M, Byrareddy SN. Drug repurposing approaches to combating viral infections. J Clin Med. 2020;9(11):3777. PMID:33238464 DOI:

Ekeomodi CC, Obetta KI, Okolocha ML, et al. Computational approaches in drug repurposing. In Rudrapal M, editor, Drug repurposing – advances, scopes and opportunities in drug discovery. IntechOpen; 2023.

Tuerkova A, Zdrazil B. A ligand-based computational drug repurposing pipeline using KNIME and Programmatic Data Access: case studies for rare diseases and COVID-19. J Cheminform. 2020;12(1):71. PMID:33250934 DOI:

Jian Hong Gan, Ji Xiang Liu, Yang Liu, et al. DrugRep: an automatic virtual screening server for drug repurposing. Acta Pharmacol Sinica. 2023;44(4):888-896. DOI:

Sadegh S, Skelton J, Anastasi E, et al. NeDRex – an integrative and interactive network medicine platform for drug repurposing. In RExPO22, The 1st International Conference on Drug Repurposing, Maastricht; 2022. DOI:

Parmar G, Chudasama JM, Shah A, Patel A. In silico pharmacology and drug repurposing approaches. In Rudrapal M, Khan J, eds, CADD and informatics in drug discovery. Springer; 2023: 253-281. DOI:

Khan S, Agnihotri J, Patil S, Khan N. Drug repurposing: a futuristic approach in drug discovery. J Pharm Biol Sci. 2023;11(1):66-69. DOI:

Geest R, Nijholt D. Hollander W. Clinical Development in Drug Repurposing. In RExPO22, The 1st International Conference on Drug Repurposing, Maastricht; ScienceOpen, August 2022.

Tan GSQ, Sloan EK, Lambert P, Kirkpatrick CMJ, Ilomäki J. Drug repurposing using real-world data. Drug Discov Today. 2023;28(1):103422. PMID:36341896 DOI:

Juárez-López D, Schcolnik-Cabrera A. Drug repurposing: considerations to surpass while re-directing old compounds for new treatments. Arch Med Res. 2021;52(3):243-251. PMID:33190955 DOI:

Selvaraj N, Swaroop AK, Nidamanuri BSS, Kumar RR, Natarajan J, Selvaraj J. Network-based drug repurposing: a critical review. Curr Drug Res Rev. 2022;14(2):116-131. PMID:35156575 DOI:

Farha MA, Brown ED. Drug repurposing for antimicrobial discovery. Nat Microbiol. 2019;4(4):565-577. PMID:30833727 DOI:

Fetro C, Scherman D. Drug repurposing in rare diseases: myths and reality. Therapie. 2020;75(2):157-160. PMID:32241561 DOI:

Aggarwal NN, Sindhoor SM, Naveen NR, Gowthami B, Biju P. Drug reprofiling: a prospective approach to battle chronic ailments. J Health Allied Sci 2023;14:38-46. DOI:

Annabell C, David R, Greaves R. Drug repurposing in cardiovascular inflammation: successes, failures, and future opportunities. Front Pharmacol. 2022;13:1046406. DOI:

Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12): 1119-1131. DOI:

Dhimolea E. Canakinumab. MAbs. 2010;2(1):3-13. PMID:20065636 DOI:

Miller J. FDA snubs Novartis bid to repurpose inflammation drug for heart attacks, October 2018.

Davis JC Jr, Heijde D, Braun J, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheumatol. 2003;48(11):3230-3236. DOI:

Gatti J, Lindstrom JA, Beitz J. Reconsideration of 2008 decision: Food and Drug Administration approval of etanercept for systemic treatment of moderate to severe pediatric psoriasis. Pediatr Dermatol. 2018;35(5):688-689. PMID:30066378 DOI:

Nathan Mewton, François Roubille, Didier Bresson et al. “Effect of colchicine on myocardial injury in acute myocardial infarction”. Circulation, vol. 144, no. 11, 859–869, 2021..

Shah B, Pillinger M, Zhong H, et al. Effects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI randomized trial. Circ Cardiovasc Interv. 2020;13(4):e008717. PMID:32295417 DOI:

Tardif J-C, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381(26):2497-2505. DOI:

Tong DC, Quinn S, Nasis A, et al. Colchicine in patients with acute coronary syndrome: the Australian COPS randomized clinical trial. Circulation. 2020;142(20):1890-1900. DOI:

Mewton N, Roubille F, Bresson D, et al. Effect of colchicine on myocardial injury in acute myocardial infarction. Circulation. 2021;144(11):859-869. PMID:34420373 DOI:

Spada A, Emami J, Sanaee F, et al. Design and evaluation of albumin nanoparticles for the delivery of a novel β-tubulin polymerization inhibitor. J Pharm Pharm Sci. 2021;24:344-362. PMID:34224665 DOI:

Kaddoura M, AlIbrahim M, Hijazi G, et al. Covid-19 therapeutic options under investigation. Vol 11. In Uckun FMM. Frontiers in pharmacology; 2020. DOI:

Ge P, Fu Y, Qi S, et al. Colchicine for prevention of post-operative atrial fibrillation: meta-analysis of randomized controlled trials. Vol 9. Front Cardiovasc Med. 2022;9:1032116. DOI:

Akrami M, Izadpanah P, Bazrafshan M, et al. Effects of colchicine on major adverse cardiac events in next 6-month period after acute coronary syndrome occurrence; a randomized placebo-control trial. BMC Cardiovasc Disord. 2021;21(1):583. PMID:34876021 DOI:

Meyer-Lindemann U, Mauersberger C, Schmidt A, et al. Colchicine impacts leukocyte trafficking in atherosclerosis and reduces vascular inflammation. Front Immunol. 2022;13:898690. DOI:

Huang W, Wang Y, Tian W, et al. Biosynthesis investigations of terpenoid, alkaloid, and flavonoid antimicrobial agents derived from medicinal plants. Antibiotics (Basel). 2022;11(10):1380. PMID:36290037 DOI:

Zhang F-S, He Q-Z, Qin CH, Little PJ, Weng JP, Xu SW. Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review. Acta Pharmacol Sin. 2022;43(9):2173-2190. PMID:35046517 DOI:

Moreira DM, Vieira JL, Gottschall CA. The effects of METhotrexate therapy on the physical capacity of patients with ISchemic heart failure: a randomized double-blind, placebo-controlled trial (METIS trial). J Card Fail. 2009;15(10):828-834. PMID:19944358 DOI:

Moreira DM, Lueneberg ME, da Silva RL, Fattah T, Gottschall CAM. MethotrexaTE THerapy in ST-segment elevation mYocardial infarctionS: a randomized double-blind, placebo-controlled trial (TETHYS Trial). J Cardiovasc Pharmacol Ther. 2017;22(6):538-545. PMID:28325070 DOI:

Ridker PM, Everett BM, Pradhan A, et al; CIRT Investigators. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2019;380(8):752-762. PMID:30415610 DOI:

Borel JF. Comparative study of in vitro and in vivo drug effects on cell-mediated cytotoxicity. Immunology. 1976;31(4):631-641. PMID:824198

Tedesco D, Haragsim L. Cyclosporine: a review. J Transplant. 2012;2012:230386. DOI:

Lim SW, Doh KC, Jin L, et al. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model. PLoS One. 2013;8(8):e72685. PMID:24009697 DOI:

Kern G, Mair SM, Noppert SJ, et al. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling. PLoS One. 2014;9(5):e96377. PMID:24816588 DOI:

Thorat A, Chou H-S, Lee C-F, et al. Effects of converting tacrolimus formulation from twice-daily to once-daily in liver transplantation recipients. BioMed Res Int. 2014;2014:265658. DOI:

Abdelkader M, Hilal M, Torky AR, Elsayed H, Allam W. Experimental study of renal toxicity of cyclosporine and the ameliorative effect of N-acetylcysteine in albino rat. Ain Shams J Forensic Med Clin Toxicol. 2021;37(2):8-15. DOI:

Cung T-T, Morel O, Cayla G, et al. Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J Med. 2015;373(11):1021-1031. PMID:26321103 DOI:

Ottani F, Latini R, Staszewsky L, et al; CYCLE Investigators. Cyclosporine A in reperfused myocardial infarction: the multicenter, controlled, open-label CYCLE trial. J Am Coll Cardiol. 2016;67(4):365-374. PMID:26821623 DOI:

Elgendy A, Alshawadfy E, Altaweel A, Elsaidi A. Cardiovascular and metabolic comorbidities of psoriasis. Dermatol Case Rep. 2016;1(1):1-9. DOI:

Sakamoto H, Kurabayashi M. Cardiovascular effects of an immunosuppressive agent cyclosporin A. Int J Immunopathol Pharmacol. 2000;15(2):75-79. PMID:12590868 DOI:

Grupper A, Shashar M, Bahry D, et al. Cyclosporine attenuates arginine transport, in human endothelial cells, through modulation of cationic amino acid transporter-1. Am J Nephrol. 2013;37(6):613-619. PMID:23796541 DOI:

Michael AA, Balakrishnan P, Velusamy T. Drug repurposing for hematological malignancies. In Sobti RC, Lal SK, Goyal RK, eds. Drug repurposing for emerging infectious diseases and cancer, Singapore, Springer; 2023:217-252. DOI:

Ioakeim-Skoufa I, Tobajas-Ramos N, Menditto E, et al. Drug repurposing in oncology: a systematic review of randomized controlled clinical trials. Cancers (Basel). 2023;15(11):2972. PMID:37296934 DOI:

Issa J-P, Garcia-Manero G, Huang X, et al. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015;121(4):556-561. PMID:25336333 DOI:

Lübbert M, Grishina O, Schmoor C, et al. Results of the randomized phase II study decider (AMLSG 14-09) comparing decitabine (DAC) with or without valproic acid (VPA) and with or without all-trans retinoic acid (ATRA) add-on in newly diagnosed elderly non-fit AML patients. Blood. 2016;128(22):589. DOI:

Tassara M, Döhner K, Brossart P, et al. Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients. Blood. 2014;123(26):4027-4036. PMID:24797300 DOI:

Wojcicki AV, Kadapakkam M, Frymoyer A, Lacayo N, Chae HD, Sakamoto KM. Repurposing drugs for acute myeloid leukemia: a worthy cause or a futile pursuit? Cancers (Basel). 2020;12(2):441. PMID:32069925 DOI:

Zong N, Chowdhury S, Zhou S, et al. Artificial intelligence-based efficacy prediction of phase 3 clinical trial for repurposing heart failure therapies. medRxiv, 2023:2023.05.25.23290531. DOI:

Turner N, Zeng X-Y, Osborne B, Rogers S, Ye J-M. Repurposing drugs to target the diabetes epidemic. Trends Pharmacol Sci. 2016;37(5):379-389. PMID:26900045 DOI:

Mandrup-Poulsen T. Perspective: testing failures. Nature. 2012;485(7398):S17. PMID:22616101 DOI:

Mantik KEK, Kim S, Gu B, et al. Repositioning of anti-diabetic drugs against dementia: insight from molecular perspectives to clinical trials. Int J Mol Sci. 2023;24(14):11450. PMID:37511207 DOI:

Pathak K, Pathak MP, Saikia R, et al. Therapeutic repurposing of antidiabetic drugs in diabetes-associated comorbidities. Curr Drug Ther. 2024;19(2):178-194. DOI:

Haddad F, Dokmak G, Bader M, Karaman R. A comprehensive review on weight loss associated with anti-diabetic medications. Life (Basel). 2023;13(4):1012. PMID:37109541 DOI:

Gussow L. More questions than answers about injectable weight loss drugs. Emerg Med News. 2023;45(7):10. DOI:

Natsheh IY, Elkhader MT, Al-Bakheit AA, et al. Inhibition of Acinetobacter baumannii biofilm formation using different treatments of silica nanoparticles. Antibiotics (Basel). 2023;12(9):1365. PMID:37760662 DOI:

Wang Y, Lu J, Engelstädter J, et al. Non-antibiotic pharmaceuticals enhance the transmission of exogenous antibiotic resistance genes through bacterial transformation. ISME J. 2020;14(8):2179-2196. PMID:32424247 DOI:

Stevenson C, Hall JP, Harrison E, Wood A, Brockhurst MA. Gene mobility promotes the spread of resistance in bacterial populations. ISME J. 2017;11(8):1930-1932. PMID:28362724 DOI:

Gillings MR, Gaze WH, Pruden A, et al. Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution. ISME J. 2015;9(6):1269-1279. DOI:

Chawla M, Verma J, Gupta R, Das B. Antibiotic potentiators against multidrug-resistant bacteria: discovery, development, and clinical relevance. Front Microbiol. 2022;13(887251):887251. PMID:35847117 DOI:

Cunningham SA, Rodriguez C, Woerther P-L, et al. In vivo emergence of dual resistance to rifampin and levofloxacin in osteoarticular Cutibacterium avidum. Microbiol Spectr. 2023;11(4):e0368722. DOI:

Dulyayangkul P, Calvopiña K, Heesom KJ, Avison MB. Novel mechanisms of efflux-mediated levofloxacin resistance and reduced amikacin susceptibility in Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2020;65(1):e01284-20. PMID:33139281 DOI:

Zając OM, Tyski S, Laudy AE. The contribution of efflux systems to levofloxacin resistance in Stenotrophomonas maltophilia clinical strains isolated in Warsaw, Poland. Biology (Basel). 2022;11(7):1044. PMID:36101423 DOI:

Ramdhani D, Azizah SN, Kusuma SAF, Sediana D. Antibiotic resistance: evaluation of levofloxacin treatment in acute respiratory tract infections cases at the Tasikmalaya City Health Center, Indonesia. J Adv Pharm Technol Res. 2020;11(3):113-116. PMID:33102193 DOI:

Trespalacios-Rangél AA, Otero W, Arévalo-Galvis A, Poutou-Piñales RA, Rimbara E, Graham DY. Surveillance of levofloxacin resistance in Helicobacter pylori isolates in Bogotá-Colombia (2009-2014). PLoS One. 2016;11(7):e0160007. PMID:27454429 DOI:

Abdelaal AM, Mahmood SS. The role of efflux pump adeJ gene in levofloxacin resistance among A. baumannii. Syst Rev Pharm. 2020;11(10):1105-1110.

Asaduzzaman M, Hasan MZ, Khatun M, et al. Resistance pattern of levofloxacin against uropathogens causing urinary tract infection in selected areas of Dhaka city. Bangladesh J Biol Agric Healthc. 2018;8(4):74-81.

Iskhakova KhI. Antibiotic sensitivity of nonfermenting gram-negative bacteria. Antibiotiki i Khimioterapiia. 1988;33(11):823-827.

Rolinson GN. Bacterial resistance to penicillins and cephalosporins. Proc R Soc Lond, B. 1971;179(1057):403-410. PMID:4401418 DOI:

Lachmajer-Lutoslawska M, Bobrowski M. Resistance to beta-lactam antibiotics Proteus strains. Acta Microbiol Pol A. 1975;8(3):141-149. PMID:1103580

Chow AW, Patten V, Guze LB. Comparative susceptibility of anaerobic bacteria to minocycline, doxycycline, and tetracycline. Antimicrob Agents Chemother. 1975;7(1):46-49. PMID:1137358 DOI:

Larsen T. Occurrence of doxycycline resistant bacteria in the oral cavity after local administration of doxycycline in patients with periodontal disease. Scand J Infect Dis. 1991;23(1):89-95. PMID:2028232 DOI:

Eliopulos N, Alsina L, Diana L, Brandl S. Multiple antimicrobial resistance in Enterobacteriaceae isolated from a Sea Lion (Otaria flavescens) specimen from Isla de Lobos, Uruguay: a case report. Brazilian J Animal Environ Res. 2022;5(4):3477-3486. DOI:

Belousoff MJ, Venugopal H, Wright A, et al. cryoEM-guided development of antibiotics for drug-resistant bacteria. ChemMedChem. 2019;14(5):527-531. PMID:30667174 DOI:

Richardson LL. Alternating antibiotics render resistant bacteria beatable. PLOS Biol. 2015;13(4):e1002105. DOI:

O’neill J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. In Review on Antimicrobial Resistance. London: Wellcome Trust; 2014.

Song M, Wu H, Wu S, et al. Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage. Biomed Pharmacother. 2016;84:1137-1143. PMID:27780143 DOI:

Alsalahat I, Al-Majdoub ZM, Taha MO, et al. Inhibition of aggregation of amyloid-β through covalent modification with benzylpenicillin; potential relevance to Alzheimer’s disease. Biochem Biophys Rep. 2021;26:100943. PMID:33778168 DOI:

Khan AN, Qureshi IA, Khan UK, Uversky VN, Khan RH. Inhibition and disruption of amyloid formation by the antibiotic levofloxacin: a new direction for antibiotics in an era of multi-drug resistance. Arch Biochem Biophys. 2021;714:109077. PMID:34728171 DOI:

Lanckohr C, Bracht H. Antimicrobial stewardship. Curr Opin Crit Care. 2022;28(5):551-556. PMID:35942707 DOI:

Rangapriya M, Lorance A, Varghese AM, Hanif A, Aruna S. Awareness and perception on antibiotics and antimicrobial resistance: a questionnaire based study. Int J Pharm Sci Rev Res. 2020;65(1):27-32. DOI:

Xiang L, Akakuru OU, Xu C, Wu A. Harnessing the intriguing properties of magnetic nanoparticles to detect and treat bacterial infections. Magnetochemistry. 2021;7(8):112. DOI:

Zhu D, Li Q, Shen Y, Zhang Q. Risk factors for quinolone-resistant Escherichia coli infection: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2020;9:11. DOI:

Bird SB, Orr PG, Mazzola JL, Brush DE, Boyer EW. Levofloxacin-related seizure activity in a patient with Alzheimer’s disease: assessment of potential risk factors. J Clin Psychopharmacol. 2005;25(3):287-288. PMID:15876916 DOI:

Doulberis M, Kotronis G, Gialamprinou D, et al. Alzheimer’s disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement. Int J Neurosci. 2021;131(3):289-301. PMID:32125206 DOI:

Mehrotra T, Devi TB, Kumar S, et al. Antimicrobial resistance and virulence in Helicobacter pylori: genomic insights. Genomics. 2021;113(6):3951-3966. PMID:34619341 DOI:

Howard R, Zubko O, Bradley R, et al; Minocycline in Alzheimer Disease Efficacy (MADE) Trialist Group. Minocycline at 2 different dosages vs placebo for patients with mild Alzheimer disease: a randomized clinical trial. JAMA Neurol. 2020;77(2):164-174. PMID:31738372 DOI:

Gandra S, Mojica N, Klein EY, et al. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis. 2016;50(50):75-82. PMID:27522002 DOI:

Narendrakumar L, Chandrika SK, Thomas S. Adaptive laboratory evolution of Vibrio cholerae to doxycycline associated with spontaneous mutation. Int J Antimicrob Agents. 2020;56(3):106097. PMID:32697966 DOI:

Kotwani A, Joshi J, Lamkang AS. Over-the-counter sale of antibiotics in India: a qualitative study of providers’ perspectives across two states. Antibiotics (Basel). 2021;10(9):1123. PMID:34572705 DOI:

Fair RJ, Tor Y. Antibiotics and Bacterial Resistance in the 21st century. Perspect. Medicin Chem; 2014;6:25-64. DOI:

Yacouba A, Olowo-Okere A, Yunusa I. Repurposing of antibiotics for clinical management of COVID-19: a narrative review. Ann Clin Microbiol Antimicrob. 2021;20(1):37-38. PMID:34020659 DOI:

Burns AL, Sleebs BE, Gancheva M, et al. Targeting malaria parasites with novel derivatives of azithromycin. Front Cell Infect Microbiol. 2022;12:1063407. PMID:36530422 DOI:

Burns AL, Sleebs BE, Siddiqui G, et al. Retargeting azithromycin analogues to have dual-modality antimalarial activity. BMC Biol.2020;18:1-23. DOI:

Gore-Langton GR, Cairns M, Compaoré YD, et al. Effect of adding azithromycin to the antimalarials used for seasonal malaria chemoprevention on the nutritional status of African children. Trop Med Int Health. 2020;25(6):740-750. DOI:

Peric M, Pešić D, Alihodžić S, et al. A novel class of fast-acting antimalarial agents: substituted 15-membered azalides. Br J Pharmacol. 2021;178(2):363-377. PMID:33085774 DOI:

Advani D, Kumar P. Therapeutic targeting of repurposed anticancer drugs in Alzheimer’s disease: using the multiomics approach. ACS Omega. 2021;6(21):13870-13887. PMID:34095679 DOI:

Tímár J, Ladányi A, Forster-Horváth C, et al. Neoadjuvant immunotherapy of oral squamous cell carcinoma modulates intratumoral CD4/CD8 ratio and tumor microenvironment: a multicenter phase II clinical trial. J Clin Oncol. 2005;23(15):3421-3432. PMID:15908653 DOI:

Avershina E, Shapovalova V, Shipulin G. Fighting antibiotic resistance in hospital-acquired infections: current state and emerging technologies in disease prevention, diagnostics and therapy. Front Microbiol. 2021;12:2044. DOI:

Tyers M, Wright GD. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat Rev Microbiol. 2019;17(3):141-155. PMID:30683887 DOI:

Hartkoorn RC, Sala C, Neres J, et al. Towards a new tuberculosis drug: pyridomycin-nature’s isoniazid. EMBO Mol Med. 2012;4(10):1032-1042. DOI:

Diacon AH, Dawson R, Groote-Bidlingmaier F, et al. Bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline. Am J Respir Crit Care Med. 2015;191(8):943-953. DOI:

Weng H-B, Chen H-X, Wang M-W. Innovation in neglected tropical disease drug discovery and development. Infect Dis Poverty. 2018;7(1):67. PMID:29950174 DOI:

Lauring AS, Andino R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog. 2010;6(7):e1001005. PMID:20661479 DOI:

Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P&T. 2015;40(4):277-283. PMID:25859123

Scherf A, Lopez-Rubio JJ, Riviere L. Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol. 2008;62:445-470. DOI:

Gomez JE, McKinney JD. M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb). 2004;84(1-2):29-44. PMID:14670344 DOI:

Barrett MP, Kyle DE, Sibley LD, Radke JB, Tarleton RL. Protozoan persister-like cells and drug treatment failure. Nat Rev Microbiol. 2019;17(10):607-620. PMID:31444481 DOI:

Donlan RM. Biofilms and device-associated infections. Emerg Infect Dis. 2001;7(2):277-281. PMID:11294723 DOI:

Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32(1):40-51. PMID:24406927 DOI:

Ginsberg AM, Spigelman M. Challenges in tuberculosis drug research and development. Nat Med. 2007;13(3):290-294. PMID:17342142 DOI:

Takuadina AI, Pazylkhan NP, Iskakov KT. Mathematical modeling of infectious diseases on the example of Astana city. Sci Educ. 2023;71.

Jiménez-Díaz MB, Mulet T, Viera S, et al. Improved murine model of malaria using Plasmodium falciparum competent strains and non-myelodepleted NOD-SCID IL2Rgammanull mice engrafted with human erythrocytes. Antimicrob Agents Chemother. 2009;53(10):4533-4536. PMID:19596869 DOI:

Aguilar C, Alves da Silva M, Saraiva M, et al. Organoids as host models for infection biology – a review of methods. Exp Mol Med. 2021;53(10):1471-1482. PMID:34663936 DOI:

Mihaljevic JR, Borkovec S, Ratnavale S, et al. SPARSEMODr: rapidly simulate spatially explicit and stochastic models of COVID-19 and other infectious diseases. Biol Methods Protocols. 2022;7(1):bpac022. DOI:

Blutt SE, Estes MK. Organoid models for infectious disease. Annu Rev Med. 2022;73(1):167-182. PMID:34644153 DOI:

Smith GC, Kao RR, Walker M. Infectious disease modelling to inform policy. Rev Sci Tech. 2023;42:173-179. PMID:37232307 DOI:

Anna PGS, Henrique dos Santos M, Banerjee A. A statistical examination of distinct characteristics influencing the performance of vector-borne epidemiological agent-based simulation models. Modelling. 2021;2(2):166-196. DOI:

Raja D. The power of epidemiological modelling in understanding and managing infectious diseases. Chettinad Health City Med J (E-2278-2044 & P-2277-8845), 2023;12(1):1-2. DOI:

Rong N, Liu J. Development of animal models for emerging infectious diseases by breaking the barrier of species susceptibility to human pathogens. Emerg Microbes Infections. 2023;12(1):2178242. DOI:

Fitzpatrick MC, Bauch CT, Townsend JP, Galvani AP. Modelling microbial infection to address global health challenges. Nat Microbiol. 2019;4(10):1612-1619. PMID:31541212 DOI:

Cartelle Gestal M, Dedloff MR, Torres-Sangiao E. Computational health engineering applied to model infectious diseases and antimicrobial resistance spread. Appl Sci (Basel). 2019;9(12):2486. DOI:

Legrand N, Ploss A, Balling R, et al. Humanized mice for modeling human infectious disease: challenges, progress, and outlook. Cell Host Microbe 2009;6(1):5-9. DOI:

Swearengen JR. Choosing the right animal model for infectious disease research. Animal Model Exp Med. 2018;1(2):100-108. PMID:30891554 DOI:



How to Cite

Natsheh, I. Y., Alsaleh, M. M., Alkhawaldeh, A. K., Albadawi, D. K., Darwish, M. M., & Shammout, M. J. A. (2024). The dark side of drug repurposing. From clinical trial challenges to antimicrobial resistance: analysis based on three major fields. Drug Target Insights, 18(1), 8–19.
Received 2024-01-02
Accepted 2024-04-18
Published 2024-05-10