SpringerLink
Log in

Biological Evaluation and Docking Study of Synthesized Derivatives of Benzotriazole and Benzimidazole as Antibacterial Agents

  • Original Article
  • Published:
Chemistry Africa Aims and scope Submit manuscript

Abstract

Background

To tackle the menace of multi-resistant bacteria which pose challenges to scientist, four benzotriazole derivatives and three benzimidazole derivatives were synthesized via two routes due to the importance of heterocyclic compound in medicinal chemistry. Two protein target DNA gyrase with PDB ID 2XCT and PDB ID 3ILW were docked with the synthesized compound and compared with the two standard drugs sparfloxacin and ciprofloxacin.

Results

For benzotriazole derivatives, the reaction in acetonitrile resulted in lower yields (18–25%) than with dimethylformamide/potassium hydroxide (DMF/KOH), which generated higher yields (68–92%) in shorter reaction time. Those of benzimidazole were comparable. The products were characterized by FTIR, 1H, and 13C NMR, while the association between atoms was shown in 2D NMR. The synthesized compounds were docked against two DNA gyrase with PDB ID 2XCT and PDB ID 3ILW. It was observed that 1-butyl-1H-benzotriazole (− 13.716) and 1-butyl-3-octyl-1H-benzotriazolium (− 12.324) were the most active against PDB ID 2XCT and PDB ID 3ILW, respectively. However, they were both less active than the standard drugs used. Using the agar diffusion technique, the synthesized compounds demonstrated broad-spectrum antibacterial activity against gram-positive and gram-negative pathogenic bacteria strains. Notably, all the compounds were of varying potency; with inhibition zones ranging from 24 to 30 mm and MIC ranging from 25 to 50 μg/mL.

Conclusions

The benzotriazole and benzimidazole derivatives were synthesized successfully. This research revealed that the synthesized compounds were active against organisms with activity, the docking results revealed that the synthesized compounds have relatively low binding energy when compared with the standard drug used as well as those reported earlier. Thus, it will give better interaction on the binding site of the protein. These synthesized compounds could be a source of new drugs that could be used to treat multi-resistance bacteria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Scheme 3
Fig. 1
Scheme 4
Scheme 5
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Not applicable.

Abbreviations

DNA:

Deoxyribonucleic acid

PDB ID:

Protein Data Bank Identity

DMF:

Dimethylformamide

KOH:

Potassium hydroxide

FTIR:

Fourier transform infrared spectroscopy

GCMS:

Gas chromatography-mass spectroscopy

TLC:

Thin layer chromatography

DMSO:

Dimethyl sulfoxide

References

  1. Zagotto G, Bortoli M (2021) Drug design: where we are and future prospects. Molecules 26(22):7061

    Article  CAS  Google Scholar 

  2. Pinzi L, Rastelli G (2019) Molecular docking: shifting paradigms in drug discovery. Int J Mol Sci. https://doi.org/10.3390/ijms20184331

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ardebili A, Pouriayevali MH, Aleshikh S, Zahani M (2021) Antiviral therapeutic potential of curcumin: an update. Molecules 26:1–23

  4. Rajasekaran S, Rao G (2012) Synthesis, antibacterial and antioxidant activity of some 2,3-susbtituted quinazolin-4(3H)-ones. Pharm Lett 4(2):470–474

    CAS  Google Scholar 

  5. Khayyat AN, Mohamed KO, Malebari AM, El-malah A (2021) Substituted imidazole-thione linked. Molecules 26:5983

    Article  CAS  Google Scholar 

  6. Datta A, Alpana A, Shrikant M, Pratyush K, Abhibnav B, Ruchita T (2020) Review on synthetic study of benzotriazole. GSC Biol Pharm Sci 11(2):215–225. https://doi.org/10.30574/gscbps.2020.11.2.0137

    Article  CAS  Google Scholar 

  7. Marinescu M (2021) Synthesis of antimicrobial benzimidazole–pyrazole compounds and their biological activities. Antibiotics (Basel, Switzerland) 10(8):1–29. https://doi.org/10.3390/antibiotics10081002

    Article  CAS  Google Scholar 

  8. Katritzky AR, Lan X, Yang JZ, Denisko OV (1998). Properties and synthetic utility of N-substituted benzotriazoles. 2665(94): 409–548

  9. Guruvelli PVS, Wagmare P, Harinath BC, Jamullamudi RN, Kurre PN, Muthyala MKK (2018) Synthesis, screening and docking analysis of novel benzimidazolium and benzotriazolium compounds as potent anti tubercular agents. Anti-Infect Agents 17(1):20–27. https://doi.org/10.2174/2211352516666180810101327

    Article  CAS  Google Scholar 

  10. Lino A, Deogracious O (2006) The in-vitro antibacterial activity of Annona senegalensis, Securidacca longipendiculata and Steganotaenia araliacea—Ugandan medicinal plants. Afr Health Sci 6(1):31–35

    PubMed  PubMed Central  Google Scholar 

  11. Sochorova R (2001) Isoquinoline alkaloids from mahonia aquifolium stem bark are active against Malassezia spp. Folia Microbiol 46(2):107–111

    Article  Google Scholar 

  12. Evans DA (2014) History of the Harvard ChemDraw Project. Angew Chemie Int Ed 53(42):11140–11145. https://doi.org/10.1002/anie.201405820

    Article  CAS  Google Scholar 

  13. Li Z, Wan H, Shi Y, Ouyang P (2004) Personal experience with four kinds of chemical structure drawing software: review on chemdraw, chemwindow, ISIS/draw, and chemsketch. J Chem Inf Comput Sci 44(5):1886–1890. https://doi.org/10.1021/ci049794h

    Article  CAS  PubMed  Google Scholar 

  14. Ruben A, Maxim T (1994) Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and protein. J Mol Biol 983–1002

  15. An J, Totrov M, Abagyan R (2005) Pocketome via comprehensive identification and classification of ligand binding envelopes. Molecular and Cellular Proteomics, 4(6):752–761. https://doi.org/10.1074/mcp.M400159-MCP200

  16. Viswanadhan VN, Ghose AK, Reyankar GR, Robins RK, Al ET (1989) Atomic Physicochemical Parameters for Three Dimensional Structure Directed Quantitative Structure-Activity Relationships . 4 . Additional Parameters for Hydrophobic and Dispersive Interactions and Their Application for an Automated Superposition of Certai. Eur J Med Chem 183:163–172

  17. Tretter EM, Schoeffler AJ, Weisfield SR, Berger JM (2009) Crystal structure of the DNA Gyrase. August, pp, 492–495. https://doi.org/10.1002/prot.22600

  18. Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, Giordano I, Hann MM, Hennessy A., Hibbs M, Huang J, Jones E, Jones J, Brown K K, Lewis CJ, May EW, Saunders MR, Singh O, Spitzfaden CE, Gwynn MN (2010) Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature, 466(7309): 935–940.https://doi.org/10.1038/nature09197

  19. Capurso M, Gette R, Radivoy G, Dorn V (2019) The Sn2 Reaction: A Theoretical-Computational Analysis of a Simple and Very Interesting Mechanism. Proceedings, 41(1):81. https://doi.org/10.3390/ecsoc-23-06514

  20. Swamy SN, Sarala G, Priya BS, Gaonkar SL, Prasad JS, Rangappa KS (2006) Microwave-assisted synthesis of N -alkylated benzotriazole derivatives : Antimicrobial studies. Bioorganic & Medicinal Chemistry Letters, 16:999–1004. https://doi.org/10.1016/j.bmcl.2005.10.084

  21. Abbas H, Niazi M, Makker J (2017) Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of the Colon: A Case Report and a Literature Review. Am J Case 18:491–497. https://doi.org/10.12659/AJCR.902843.

  22. Bairam R, Muppavarapu SM, Sreekanth S (2017) SYNTHESIS , CHARACTERIZATION , BIOLOGICAL EVALUATION AND DOCKING OF SOME NOVEL SUBSTITUTED 1 , 3-THIAZINE DERIVATIVES. International Journal of Pharmacy and Pharmaceutical Sciences, 9(3):233–242.

  23. Hameed S, Seraj F, Ra R, Chigurupati S (2019) Synthesis of benzotriazoles derivatives and their dual potential as a-amylase and a-glucosidase inhibitors in vitro : Structure-activity relationship, molecular docking, and kineti studies. Eur. J Med Chem 183. https://doi.org/10.1016/j.ejmech.2019.111677

Download references

Acknowledgements

The authors are grateful to Mall. Abdullahi Mikaila of Nigeria Institute of Leather Technology (NILET) Zaria, Kaduna State, Nigeria for the antimicrobial activity studies and Mall. Jafar of Multi-User Laboratory, Ahmadu Bello University, Zaria Kduna State, Nigeria for the spectroscopic analysis. Finally, I will like to acknowledge Dr. Abdulfatai Usman, Mall. Abduljelil Ajala and Mall. Zakari Yau Ibrahim for their advice.

Funding

No any form of fund was received from any organization.

Author information

Author notes

  1. Tajudeen A. Jimoh

    Present address: Chemistry Department, Al-Qalam University, IBB Way Dutsinma Road, PMB 2137, Katsina, Katsina, Nigeria

Authors and Affiliations

  1. Chemistry Department, Ahmadu Bello University, Samaru, PMB 1044, Zaria, Kaduna, Nigeria

    Tajudeen A. Jimoh, Adebayo O. Oyewale, Hamisu Ibrahim & James D. Habila

  2. Chemistry Department, University of Maiduguri, Bama Road, PMB 1069, Maiduguri, Borno, Nigeria

    David.E. Arthur

Authors
  1. Tajudeen A. Jimoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adebayo O. Oyewale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hamisu Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James D. Habila
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David.E. Arthur
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TAJ. and Prof. AOO.: design the experiment and carry out the synthesis of the compounds. Dr. HI. and Dr. JDH.: write the manuscript and proofread the manuscript. Dr. DEA.: docked the synthesized compound against the target protein.

Corresponding author

Correspondence to Tajudeen A. Jimoh.

Ethics declarations

Conflict of interest

No competing interest.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jimoh, T.A., Oyewale, A.O., Ibrahim, H. et al. Biological Evaluation and Docking Study of Synthesized Derivatives of Benzotriazole and Benzimidazole as Antibacterial Agents. Chemistry Africa 5, 509–523 (2022). https://doi.org/10.1007/s42250-022-00348-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42250-022-00348-x

Keywords

Search

Navigation