Comparative potential of Simvastatin, Rosuvastatin and Fluvastatin against bacterial infection: an in silico and in vitro study

  • Meenakshi Gupta
  • Ruchika Sharma
  • Anoop KumarEmail author
Research Article


In the current investigation, we have compared the potential of statin drugs (Simvastatin, Rosuvastatin and Fluvastatin) as potential anti-bacterial agent by conducting in silico, in vitro and ex vivo studies. In silico study was conducted to check the interaction of statin drugs towards various targets of bacteria. The percentage growth retardation, bacterial growth kinetics, MIC determination, post antibiotic effect and biofilm formation assay were conducted to check the anti-bacterial effect of statin drugs under in vitro conditions. Finally, MTT assay was used to check the percentage of immune cell viability after Simvastatin treatment. Docking studies have revealed good interaction of Simvastatin, Rosuvastatin and Fluvastatin towards various targets of bacterial strains as that of the internal ligand. Simvastatin has shown good antibacterial activity against S. aureus, B. pumilus, P. aeruginosa and S. enterica as compared to Rosuvastatin and Fluvastatin. In vitro results have shown concentration and time dependent inhibition of bacterial growth by Simvastatin in concentration range of 64–256 μg/ml. Finally, MTT assay have shown non-cytotoxic effect of Simvastatin against adaptive immune system. In conclusion, Simvastatin could be a potential candidate as an anti-bacterial agent against a wide range of bacterial infections. However, further studies are required to check its complete role before starting phase I clinical trial.


Simvastatin Rosuvastatin Fluvastatin Docking study Bacterial infections Antibiotics 



Authors are thankful to Shri. Parveen Garg, Chairman, ISFCP, for providing research facility. Authors are thankful to Mr. Saurabh Bhandari, Assistant Professor, Microbiology Division, ISFCP, Moga for providing support in completion of this research work. Authors are also thankful to Mr. Anshul Ruhela, B.Tech., Ansal University, for graphic enhancement of images. Author, Anoop Kumar is also thankful to Dr. S.J.S. Flora, Director, NIPER, Raebareli for their constant support and motivation.

Compliance with ethical standards

Ethical statement

Animal house is registered with the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India. Registration number: 816/Po/Re/S/04/CPCSEA.

Conflict of interest

This manuscript described has not been published before; not under consideration for publication anywhere else; and has been approved by all co-authors.


  1. Bannister RM, Wanderlay WC, Brew J (2010) Treatment of microbial infections. Biocopea Limited. U.S. Patent Application. 13/509:534Google Scholar
  2. Bradbury BJ, Pucci MJ (2008) Recent advances in bacterial topoisomerase inhibitors. Curr Opin Pharmacol 8:574–581. CrossRefGoogle Scholar
  3. Caldwell JR, Cluff LE (1974) Adverse reactions to antimicrobial agents. JAMA 230:77–80. CrossRefGoogle Scholar
  4. Chow OA, von Köckritz-Blickwede M, Bright AT, Hensler ME, Zinkernagel AS, Cogen AL (2010) Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe 8:445–454. CrossRefGoogle Scholar
  5. Cohen ML (1992) Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 257:1050–1055. CrossRefGoogle Scholar
  6. Craig WA (1996) Post-antibiotic effect. Antibiotics in laboratory medicine, 4th edn. Williams and Wilkins Co., BaltimoreGoogle Scholar
  7. Davignon J, Jacob RF, Mason RP (2004) The antioxidant effects of statins. Coron Artery Dis 15:251–258. CrossRefGoogle Scholar
  8. Donowitz GR, Mandell GL (1988) Beta-lactam antibiotics. N Engl J Med 318:490–500. CrossRefGoogle Scholar
  9. Eliopoulos GM, Roberts MC (2003) Tetracycline therapy: update. Clin Infect Dis 36:462–467. CrossRefGoogle Scholar
  10. Graziano TS, Cuzzullin MC, Franco GC, Schwartz-Filho HO, de Andrade ED, Groppo FC (2015) Statins and antimicrobial effects: simvastatin as a potential drug against Staphylococcus aureus biofilm. PLoS ONE 10:0128098. CrossRefGoogle Scholar
  11. Grewal GK, Rawal RK (2014) Molecular docking studies on (hetero) arlylidene (4-substituted-thiazol-2-yl) hydrazines as MAO-B inhibitors. Asian J Biomed Pharm Sci 4:56Google Scholar
  12. Gupta M, Kumar A (2019) Comparison of minimum inhibitory concentration (MIC) value of statin drugs: a systematic review. Anti-Infect Agents. Google Scholar
  13. Gupta M, Sharma R, Kumar A (2018a) Docking techniques in pharmacology: how much promising? Comput Biol Chem 76:210–217. CrossRefGoogle Scholar
  14. Gupta M, Kant K, Sharma R, Kumar A (2018b) Evaluation of in silico anti-parkinson potential of β-asarone. Cent Nerv Syst Agents Med Chem 18:128–135. CrossRefGoogle Scholar
  15. Hawser S, Lociuro S, Islam K (2006) Dihydrofolate reductase inhibitors as antibacterial agents. Biochem Pharmacol 71:41–948. CrossRefGoogle Scholar
  16. Hennessy E, Adams C, Reen FJ, O’Gara F (2016) Is there potential for repurposing statins as novel antimicrobials? Antimicrob Agents Chemother 60:5111–5121. CrossRefGoogle Scholar
  17. Jacobson TA (2006) Statin safety: lessons from new drug applications for marketed statins. Am J Cardiol 97:S44–S51. CrossRefGoogle Scholar
  18. Jaiswal S, Duffy B, Jaiswal AK, Stobie N, McHale P (2010) Enhancement of the antibacterial properties of silver nanoparticles using β-cyclodextrin as a capping agent. Int J Antimicrob Agents 36:280–283. CrossRefGoogle Scholar
  19. Jouneau S, Bonizec M, Belleguic C, Desrues B, Brinchault G, Galaine J (2011) Anti-inflammatory effect of fluvastatin on IL-8 production induced by Pseudomonas aeruginosa and Aspergillus fumigatus antigens in cystic fibrosis. PLoS ONE 6:22655. CrossRefGoogle Scholar
  20. Kamińska M, Aliko A, Hellvard A, Marczyk A, Mydel P (2017) Effects of statins on multispecies oral biofilm. J Oral Microbiol 9:1325249. CrossRefGoogle Scholar
  21. Kohanski MA, Dwyer DJ, Collins JJ (2010) How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol 8:423CrossRefGoogle Scholar
  22. Kumar A, Sasmal D, Sharma N (2014) Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes: exploring the molecular mechanism. J Appl Toxicol 34:1303–1310. CrossRefGoogle Scholar
  23. Kumar A, Sasmal D, Sharma N (2018) Mechanism of deltamethrin induced thymic and splenic toxicity in mice and its protection by piperine and curcumin: in vivo study. Drug Chem Toxicol 41:33–41. CrossRefGoogle Scholar
  24. Langfield RD, Scarano FJ, Heitzman ME, Kondo M, Hammond GB, Neto C (2004) Use of a modified microplate bioassay method to investigate antibacterial activity in the Peruvian medicinal plant Peperomiagalioides. J Ethnopharmacol 94:279–281. CrossRefGoogle Scholar
  25. Lefer DJ (2011) Statins as potent anti-inflammatory drugs. Circ Res 106:2041–2042. CrossRefGoogle Scholar
  26. Mach F (2002) Toward a role for statins in immunomodulation. Mol Interv 2:478. CrossRefGoogle Scholar
  27. Masadeh M, Mhaidat N, Alzoubi K, Al-azzam S, Alnasser Z (2012) Antibacterial activity of statins: a comparative study of atorvastatin, Simvastatin, and rosuvastatin. Ann Clin Microbiol Antimicrob 11:13–18. CrossRefGoogle Scholar
  28. Morgan S, Grootendorst P, Lexchin J, Cunningham C, Greyson D (2011) The cost of drug development: a systematic review. Health Policy 100:4–17. CrossRefGoogle Scholar
  29. Mullin R (2014) Cost to develop new pharmaceutical drug now exceeds $2.5 B. Sci Am 24:1–2Google Scholar
  30. NCCLS (2006) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7eA7. Clinical and laboratory Standards Institute, WayneGoogle Scholar
  31. Oprea TI, Mestres J (2012) Drug repurposing: far beyond new targets for old drugs. AAPS J 14:759–763. CrossRefGoogle Scholar
  32. Raja AF, Ali F, Khan IA, Shawl AS, Arora DS, Shah BA (2011) Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-beta-boswellic acid from Boswelliaserrata. BMC Microbial 11:54. CrossRefGoogle Scholar
  33. Stancu C, Sima A (2001) Statins: mechanism of action and effects. J Cell Mol Med 25:378–387. CrossRefGoogle Scholar
  34. Tabish SA, Syed N (2015) The future of humanity and microbes: impact of emerging infectious diseases on global health and economies. Int J Pharm Sci Res 4:2427–2442Google Scholar
  35. Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP (2011) Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. Google Scholar
  36. Thangamani S, Mohammad H, Abushahba MF, Hamed MI, Sobreira TJ, Hedrick VE (2015) Exploring Simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. Sci Rep 5:16407CrossRefGoogle Scholar
  37. Tobinick EL (2009) The value of drug repositioning in the current pharmaceutical market. Drug News Perspect 22:119–125CrossRefGoogle Scholar
  38. Verdonk ML, Cole JC, Hartshorn MJ, Murray CW, Taylor RD (2003) Improved protein–ligand docking using GOLD. Proteins Struct Funct Bioinf 52:609–623. CrossRefGoogle Scholar
  39. Who G (2013) WHO methods and data sources for global burden of disease estimates 2000–2011. Department of Health Statistics and Information Systems, GenevaGoogle Scholar
  40. Wu WS, Chen CC, Chuang YC, Su BA, Chiu YH, Hsu HJ (2013) Efficacy of combination oral antimicrobial agents against biofilm-embedded methicillin-resistant Staphylococcus aureus. J Microbiol Immunol Infect 46:89–95. CrossRefGoogle Scholar
  41. Yang JH, Bhargava P, McCloskey D, Mao N, Palsson BO, Collins JJ (2017) Antibiotic-induced changes to the host metabolic environment inhibit drug efficacy and alter immune function. Cell Host Microbe 22:757–765. CrossRefGoogle Scholar

Copyright information

© Institute of Korean Medicine, Kyung Hee University 2019

Authors and Affiliations

  1. 1.Department of PharmacologyIndo-Soviet Friendship College of Pharmacy (ISFCP)MogaIndia
  2. 2.Department of BiotechnologyIndo-Soviet Friendship College of Professional Studies (ISFCPS)MogaIndia
  3. 3.Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and Research (NIPER)-RaebareliLucknowIndia

Personalised recommendations