Antimicrobial activities of Diltiazem Hydrochloride: drug repurposing approach.

Omar K Alduaij, Rageh K Hussein, Sharif Abu Alrub, Sabry A H Zidan
Author Information
  1. Omar K Alduaij: Department of Physics, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
  2. Rageh K Hussein: Department of Physics, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
  3. Sharif Abu Alrub: Department of Physics, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
  4. Sabry A H Zidan: Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut-Branch, Assiut, Egypt.

Abstract

Background: The growing concern of antibiotic-resistant microbial strains worldwide has prompted the need for alternative methods to combat microbial resistance. Biofilm formation poses a significant challenge to antibiotic efficiency due to the difficulty of penetrating antibiotics through the sticky microbial aggregates. Drug repurposing is an innovative technique that aims to expand the use of non-antibiotic medications to address this issue. The primary objective of this study was to evaluate the antimicrobial properties of Diltiazem HCl, a 1,5-benzothiazepine Ca channel blocker commonly used as an antihypertensive agent, against four pathogenic bacteria and three pathogenic yeasts, as well as its antiviral activity against the Coxsackie B4 virus (CoxB4).
Methods: To assess the antifungal and antibacterial activities of Diltiazem HCl, the well diffusion method was employed, while crystal violet staining was used to determine the anti-biofilm activity. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay was utilized to evaluate the antiviral activity of Diltiazem HCl against the CoxB4 virus.
Results: This study revealed that Diltiazem HCl exhibited noticeable antimicrobial properties against Gram-positive bacteria, demonstrating the highest inhibition of , followed by . It effectively reduced the formation of biofilms by 95.1% and 90.7% for , and , respectively. Additionally, the antiviral activity of Diltiazem HCl was found to be potent against the CoxB4 virus, with an IC of 35.8 �� 0.54 ��g mL compared to the reference antiviral Acyclovir (IC 42.71 �� 0.43 ��g mL).
Conclusion: This study suggests that Diltiazem HCl, in addition to its antihypertensive effect, may also be a potential treatment option for infections caused by Gram-positive bacteria and the CoxB4 viruses, providing an additional off-target effect for Diltiazem HCl.

Keywords

References

  1. Adv Biomed Res. 2013 Mar 30;2:36 [PMID: 24516836]
  2. Molecules. 2023 May 12;28(10): [PMID: 37241788]
  3. Int J Med Microbiol. 2002 Jul;292(2):107-13 [PMID: 12195733]
  4. Molecules. 2022 Oct 29;27(21): [PMID: 36364194]
  5. J Ethnopharmacol. 2009 Jul 30;124(3):457-62 [PMID: 19481144]
  6. Anticancer Agents Med Chem. 2023;23(10):1104-1121 [PMID: 35379128]
  7. Eur J Med Chem. 2017 Jan 5;125:657-662 [PMID: 27721151]
  8. Br J Cancer. 2024 Mar;130(5):703-715 [PMID: 38012383]
  9. Indian J Pediatr. 2001 Jul;68(7):655-68 [PMID: 11519290]
  10. Acta Pol Pharm. 2008 Nov-Dec;65(6):779-82 [PMID: 19172867]
  11. Front Microbiol. 2024 Feb 20;15:1370818 [PMID: 38444801]
  12. Front Pharmacol. 2024 Jun 07;15:1397602 [PMID: 38910882]
  13. Life (Basel). 2023 Aug 04;13(8): [PMID: 37629545]
  14. Sci Rep. 2022 Nov 10;12(1):19239 [PMID: 36357560]
  15. Viruses. 2020 Mar 28;12(4): [PMID: 32231022]
  16. Front Immunol. 2019 Jan 29;10:60 [PMID: 30761132]
  17. J Bacteriol. 2005 Jul;187(13):4327-37 [PMID: 15968041]
  18. Cell Host Microbe. 2018 Jun 13;23(6):809-818.e5 [PMID: 29779930]
  19. Can J Surg. 2006 Apr;49(2):101-6 [PMID: 16630420]
  20. Eur J Med Chem. 2008 Nov;43(11):2279-90 [PMID: 18639369]
  21. Sci Rep. 2024 Feb 7;14(1):3183 [PMID: 38326360]
  22. Antiviral Res. 2020 Sep;181:104878 [PMID: 32679055]
  23. Cells. 2023 Feb 20;12(4): [PMID: 36831338]
  24. Fitoterapia. 2020 Nov;147:104765 [PMID: 33122132]
  25. Recent Adv Antiinfect Drug Discov. 2023;18(3):205-214 [PMID: 36345239]
  26. Antiviral Res. 2005 Aug;67(2):98-106 [PMID: 16054245]
  27. Pharmacol Rep. 2020 Dec;72(6):1479-1508 [PMID: 32889701]
  28. Viral Immunol. 2004;17(3):358-69 [PMID: 15357902]
  29. FEMS Immunol Med Microbiol. 2010 Mar;58(2):237-43 [PMID: 19930457]
  30. Front Pharmacol. 2017 May 29;8:286 [PMID: 28611661]
  31. J Chemother. 2009 Apr;21(2):135-43 [PMID: 19423465]
  32. Front Microbiol. 2020 Jun 23;11:1143 [PMID: 32655511]

MeSH Term

Diltiazem
Biofilms
Antiviral Agents
Drug Repositioning
Microbial Sensitivity Tests
Humans
Anti-Bacterial Agents
Enterovirus B, Human
Staphylococcus aureus
Calcium Channel Blockers
Staphylococcus epidermidis
Anti-Infective Agents
Antifungal Agents
Gram-Positive Bacteria

Chemicals

Diltiazem
Antiviral Agents
Anti-Bacterial Agents
Calcium Channel Blockers
Anti-Infective Agents
Antifungal Agents

Word Cloud

Created with Highcharts 10.0.0DiltiazemHClantiviralactivityCoxB4microbialrepurposingstudybacteriavirusformationDrugevaluateantimicrobialpropertiesusedantihypertensivepathogenicwellCoxsackieactivitiesMTTGram-positiveIC��0��gmLeffectStaphBackground:growingconcernantibiotic-resistantstrainsworldwidepromptedneedalternativemethodscombatresistanceBiofilmposessignificantchallengeantibioticefficiencyduedifficultypenetratingantibioticsstickyaggregatesinnovativetechniqueaimsexpandusenon-antibioticmedicationsaddressissueprimaryobjective15-benzothiazepineCachannelblockercommonlyagentfourthreeyeastsB4Methods:assessantifungalantibacterialdiffusionmethodemployedcrystalvioletstainingdetermineanti-biofilm3-45-dimethylthiazol-2-yl-25-diphenyltetrazoliumbromidecolorimetricassayutilizedResults:revealedexhibitednoticeabledemonstratinghighestinhibitionfollowedeffectivelyreducedbiofilms951%907%respectivelyAdditionallyfoundpotent35854comparedreferenceAcyclovir427143Conclusion:suggestsadditionmayalsopotentialtreatmentoptioninfectionscausedvirusesprovidingadditionaloff-targetAntimicrobialHydrochloride:drugapproachAntibacterialAntibioticsAntiviralaureusepidermidisantibiofilm

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