Repurposing of Existing Drugs for the Bacterial Infections: An In silico and In vitro Study

Author(s): Yachika Kapoor, Ruchika Sharma, Anoop Kumar*

Journal Name: Infectious Disorders - Drug Targets
(Formerly Current Drug Targets - Infectious Disorders)

Volume 20 , Issue 2 , 2020

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Graphical Abstract:


Abstract:

Background: The emergence of infectious diseases and its resistance to approved drugs is a global threat to human health. The incidence of infectious diseases is increasing day by day and expected to rise exponentially in next 2 decades. Thus, there is a need for new treatment modalities for the treatment of microbial infections.

Methods: Thus, in the current investigation, we have explored the existing drugs [metformin (Anti-diabetic), propranolol (Anti-hypertensive) and amitriptyline (antidepressant)] for treatment of infectious diseases.

Results: An in-silico result of current investigation has shown the good interaction of metformin, propranolol, and amitriptyline towards various targets (Beta-lactamase, Penicillin-binding proteins, Staphylokinase protein, Oxidoreductase protein, etc.) of gram positive and gram negative bacteria as that of internal ligand. Further, in-vitro results have shown that the antibacterial activity of metformin, propranolol, and amitriptyline against Bacillus pumilus, Pseudomonas aeruginosa and Staphylococcus aureus.

Conclusion: The parameters such as Microtiter assay: percentage growth retardation and bacterial growth kinetics, Minimum inhibitory concentration (MIC), Post-antibiotic assay and Biofilm formation have indicated the antibacterial potential of metformin, propranolol, and amitriptyline. However, before starting a clinical trial, complete safety and efficacy profile of drugs in the treatment of infectious diseases should be investigated.

Keywords: Infectious diseases, drug repurposition, In silico, In vitro studies, bacterial infections, metformin, propranolol.

[1]
Khasnis, A.A.; Nettleman, M.D. Global warming and infectious disease. Arch. Med. Res., 2005, 36(6), 689-696.
[http://dx.doi.org/10.1016/j.arcmed.2005.03.041] [PMID: 16216650]
[2]
Lopez, A.D.; Mathers, C.D.; Ezzati, M.; Jamison, D.T.; Murray, C.J. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet, 2006, 367(9524), 1747-1757.
[http://dx.doi.org/10.1016/S0140-6736(06)68770-9] [PMID: 16731270]
[3]
Lee, H.H.; Collins, J.J. Microbial environments confound antibiotic efficacy. Nat. Chem. Biol., 2011, 8(1), 6-9.
[http://dx.doi.org/10.1038/nchembio.740] [PMID: 22173343]
[4]
Merritt, T.H.; Segreti, J. The role of the infectious disease specialist in the and treatment of primary immunodeficiency disease. Infect. Dis. Clin. Pract., 2011, 19, 316-325.
[http://dx.doi.org/10.1097/IPC.0b013e318214b068]
[5]
Ferri, M.; Ranucci, E.; Romagnoli, P.; Giaccone, V. Antimicrobial resistance: A global emerging threat to public health systems. Crit. Rev. Food Sci. Nutr., 2017, 57(13), 2857-2876.
[http://dx.doi.org/10.1080/10408398.2015.1077192] [PMID: 26464037]
[6]
Boucher, H.W.; Talbot, G.H.; Bradley, J.S.; Edwards, J.E.; Gilbert, D.; Rice, L.B.; Scheld, M.; Spellberg, B.; Bartlett, J. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis., 2009, 48(1), 1-12.
[http://dx.doi.org/10.1086/595011] [PMID: 19035777]
[7]
Rana, R.; Sharma, R.; Kumar, A. Repurposing of Existing Statin drugs for treatment of Microbial Infections: How much Promising? Infect. Disord. Drug Targets, 2018.
[http://dx.doi.org/10.2174/1871526518666180806123230] [PMID: 30081793]
[8]
Li, J.; Zheng, S.; Chen, B.; Butte, A.J.; Swamidass, S.J.; Lu, Z. A survey of current trends in computational drug repositioning. Brief. Bioinform., 2016, 17(1), 2-12.
[http://dx.doi.org/10.1093/bib/bbv020] [PMID: 25832646]
[9]
Malik, F.; Mehdi, S.F.; Ali, H.; Patel, P.; Basharat, A.; Kumar, A.; Ashok, F.; Stein, J.; Brima, W.; Malhotra, P.; Roth, J. Is metformin poised for a second career as an antimicrobial? Diabetes Metab. Res. Rev., 2018, 34(4)e2975
[http://dx.doi.org/10.1002/dmrr.2975] [PMID: 29271563]
[10]
Hadera, M.; Mehari, S.; Basha, N.S. Study on Antimicrobial Potential of Selected Non-antibiotics and its Interaction with Conventional Antibiotics. UK Journal of Pharmaceutical and Biosciences, 2018, 6, 2-7.
[http://dx.doi.org/10.20510/ukjpb/6/i1/173522]
[11]
Mandal, A.; Sinha, C.; Kumar Jena, A.; Ghosh, S.; Samanta, A. An investigation on in vitro and in vivo antimicrobial properties of the antidepressant: amitriptyline hydrochloride. Braz. J. Microbiol., 2010, 41(3), 635-645.
[http://dx.doi.org/10.1590/S1517-83822010000300014] [PMID: 24031539]
[12]
Hassan, A.N.; Frank, J.F. Attachment of Escherichia coli O157:H7 grown in tryptic soy broth and nutrient broth to apple and lettuce surfaces as related to cell hydrophobicity, surface charge, and capsule production. Int. J. Food Microbiol., 2004, 96(1), 103-109.
[http://dx.doi.org/10.1016/S0168-1605(03)00160-0] [PMID: 15358511]
[13]
Langfield, R.D.; Scarano, F.J.; Heitzman, M.E.; Kondo, M.; Hammond, G.B.; Neto, C.C. Use of a modified microplate bioassay method to investigate antibacterial activity in the Peruvian medicinal plant Peperomia galioides. J. Ethnopharmacol., 2004, 94(2-3), 279-281.
[http://dx.doi.org/10.1016/j.jep.2004.06.013] [PMID: 15325731]
[14]
Jaiswal, S.; Duffy, B.; Jaiswal, A.K.; Stobie, N.; McHale, P. Enhancement of the antibacterial properties of silver nanoparticles using beta-cyclodextrin as a capping agent. Int. J. Antimicrob. Agents, 2010, 36(3), 280-283.
[http://dx.doi.org/10.1016/j.ijantimicag.2010.05.006] [PMID: 20580208]
[15]
Performance Standards for Antimicrobial Disk Susceptibility Tests;Approved Standard-Eleventh Edition. In: CLSI document M02-A11. Wayne, PA: Clinical and Laboratory Standards Institute; , 2012; 32, pp. 3-5.
[16]
Gupta, M.; Kumar, A. Comparison of Minimum Inhibitory Concentration (MIC) value of statin drugs: A Systematic Review. Antiinfect. Agents, 2018, 124433
[http://dx.doi.org/10.2174/2211352516666180629124433]
[17]
LiPuma, J.J.; Rathinavelu, S.; Foster, B.K.; Keoleian, J.C.; Makidon, P.E.; Kalikin, L.M.; Baker, J.R., Jr In vitro activities of a novel nanoemulsion against Burkholderia and other multidrug-resistant cystic fibrosis-associated bacterial species. Antimicrob. Agents Chemother., 2009, 53(1), 249-255.
[http://dx.doi.org/10.1128/AAC.00691-08] [PMID: 18955531]
[18]
Raja, A.F.; Ali, F.; Khan, I.A.; Shawl, A.S.; Arora, D.S.; Shah, B.A.; Taneja, S.C. Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-β-boswellic acid from Boswellia serrata. BMC Microbiol., 2011, 11, 54.
[http://dx.doi.org/10.1186/1471-2180-11-54] [PMID: 21406118]
[19]
Peeters, E.; Nelis, H.J.; Coenye, T. Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates. J. Microbiol. Methods, 2008, 72(2), 157-165.
[http://dx.doi.org/10.1016/j.mimet.2007.11.010] [PMID: 18155789]
[20]
Rana, D.; Kumar, A. Is there a Role for Sodium Orthovanadate in the Treatment of Diabetes? Curr. Diabetes Rev., 2018, 14, 15-26.
[PMID: 30179137]
[21]
Propranolol, S.D.G. N. Engl. J. Med., 1975, 293, 280-285.
[http://dx.doi.org/10.1056/NEJM197508072930606] [PMID: 1094291]
[22]
Biederman, J.; Herzog, D.B.; Rivinus, T.M.; Harper, G.P.; Ferber, R.A.; Rosenbaum, J.F.; Harmatz, J.S.; Tondorf, R.; Orsulak, P.J.; Schildkraut, J.J. Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study. J. Clin. Psychopharmacol., 1985, 5(1), 10-16.
[http://dx.doi.org/10.1097/00004714-198502000-00003] [PMID: 3973067]
[23]
Gupta, M.; Sharma, R.; Kumar, A. Docking techniques in pharmacology: How much promising? Comput. Biol. Chem., 2018, 76, 210-217.
[http://dx.doi.org/10.1016/j.compbiolchem.2018.06.005] [PMID: 30067954]
[24]
Gupta, M; Kant, K; Sharma, R. Evaluation of in silico antiparkinson potential of β-asarone. Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Central Nervous System Agents), 2018, 18, 128-135.
[25]
Dash, A.; Behera, S.; Pattanaik, B. Study of antimicrobial property of some hypoglycemic drugs. Chronicles of Young Scientists, 2011, 2, 219-219.
[http://dx.doi.org/10.4103/2229-5186.93029]
[26]
Abruzzo, A.; Bigucci, F.; Cerchiara, T. Mucoadhesive chitosan/gelatin films for buccal delivery of propranolol hydrochloride. Carbohydr. Polym., 2012, 87, 581-588.
[http://dx.doi.org/10.1016/j.carbpol.2011.08.024]
[27]
Abbas, H.A.; Elsherbini, A.M.; Shaldam, M.A. Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa. Afr. Health Sci., 2017, 17(3), 808-819.
[http://dx.doi.org/10.4314/ahs.v17i3.24] [PMID: 29085409]
[28]
Nałecz-Jawecki, G. Spirotox-Spirostomum ambiguum acute toxicity test-10 years of experience. Environ. Toxicol., 2004, 19(4), 359-364.
[http://dx.doi.org/10.1002/tox.20023] [PMID: 15269908]


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Article Details

VOLUME: 20
ISSUE: 2
Year: 2020
Page: [182 - 197]
Pages: 16
DOI: 10.2174/1871526519666181126094244
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