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Some Benzotriazole and Benzimidazole Derivatives as Antifungal Agents for Candida Species: A Molecular Docking Study

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Abstract

Background

The efficacy of azole drugs has been reduced due to the emergence of drug resistant fungal pathogens. Despite this, heterocyclic compounds are still regarded as a viable lead structure for the synthesis of a more effective antimicrobial agent. The synthesized derivatives were screened in vitro against some fungal organisms. The synthesized compounds were docked to CYP51, a member of the cytochrome P450 family 51 sub-family A. (PDB ID: 5JLC) to determine its most favorable conformation and the energy-maximizing and minimizing orientation.

Results

The efficacy of seven derivatives of benzotriazole and benzimidazole each against some Candida species varied, with inhibition zones ranging from 24 to 37 mm and MICs from 25 to 50 g/mL. The molecular docking study of the synthesized compounds with target CYP51 is a member of the cytochrome P450 family 51 sub-family A. (PDB ID: 5JLC). 1,3-dioctyl-1H-benzimidazol-3-ium gave the best docking score of − 22.79, slightly below the standard drug (fluconazole) used with a docking score of − 22.73 when docked with CYP 51 with PDB ID: 5JLC. The p value obtained using ANOVA analysis of the zone of inhibition for compound 5 was 0.018099 which is less than 0.05, thus confirming it as the most active compound against the Candida species.

Conclusion

According to the study, 1,3-dioctyl-1H-benzimidazol-3-ium (compound 5) showed the highest antifungal activity with maximum zone of inhibition of 37 mm, minimum inhibitory concentration of 6.25 g/mL, and minimum fungicidal concentration of 25 g/mL against Candida stellatoidea. The docking study confirmed that the 1,3-dioctyl-1H-benzimidazol-3-ium had a greater binding affinity of − 22.79 kcal/mol than the other synthesized derivatives as well as the control drug, fluconazole.

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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.

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Author notes

  1. Tajudeen A. Jimoh

    Present address: Chemistry Department, Al-Qalam University Katsina, IBB Way Dutsinma Road, P.M.B 2137, Katsina, Katsina State, Nigeria

  2. Adebayo O. Oyewale, Hamisu Ibrahim & James D. Habila

    Present address: Chemistry Department, Ahmadu Bello University, P.M.B 1044, Samaru, Zaria, Kaduna State, Nigeria

Authors and Affiliations

  1. Chemistry Department, Ahmadu Bello University, P.M.B 1044, Samaru, Zaria, Kaduna State, Nigeria

    Tajudeen A. Jimoh

  2. Chemistry Department, University of Maiduguri, Bama Road, P.M.B 1069, Maiduguri, Borno State, Nigeria

    David E. Arthur

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  1. Tajudeen A. Jimoh
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Contributions

T.A.J. and Prof. A.O.O.: Design the experiment and carry out the synthesis of the compounds. Dr. H.I. and Dr. J.D.H.: write the manuscript and proofread the manuscript. Dr. D.E.A.: Docked the synthesized compound against the target protein.

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Correspondence to Tajudeen A. Jimoh.

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Jimoh, T.A., Oyewale, A.O., Ibrahim, H. et al. Some Benzotriazole and Benzimidazole Derivatives as Antifungal Agents for Candida Species: A Molecular Docking Study. Chemistry Africa 6, 383–391 (2023). https://doi.org/10.1007/s42250-022-00498-y

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