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In silico identification of 1,2,4-triazoles as potential Candida Albicans inhibitors using 3D-QSAR, molecular docking, molecular dynamics simulations, and ADMET profiling

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Abstract

Fluconazole and Voriconazole are individual antifungal inhibitors broadly adopted for treating fungal infections, including Candida Albicans. Unfortunately, these medicines clinically used have significant side effects. Consequently, the improvement of safer and better therapy became more indispensable. In this study, a set of 27 1,2,4-triazole compounds have been tested as potential Candida Albicans inhibitors by using different theoretical methods. The created comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) contour maps significantly impacted the development of novel Candida Albicans inhibitors with valuable activities. The mode of interactions between the 1,2,4-triazole inhibitors and the targeted receptor was studied by molecular docking simulation. The proposed new molecule P1 showed satisfied stability in the active pocket of the targeted receptor compared to the more active molecule in the dataset compared to Fluconazole medication. Meanwhile, the binding energy obtained by molecular docking for molecule P1 is − 9.3 kcal/mol compared with − 6.7 kcal/mol for Fluconazole medication. Also, MM/GBSA value obtained by molecular dynamics simulations at 100 ns for molecule P1 is − 33.34 kcal/mol compared with − 15.85 kcal/mol for Fluconazole medication. In addition, molecule P1 showed good oral bioavailability and was non-toxic according to ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties. Therefore, the results indicated compound P1 might be a future inhibitor of Candida Albicans infection.

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Acknowledgements

We dedicate this work to the “Moroccan Association of Theoretical Chemists” (MATC) for its pertinent help concerning the programs.

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Authors and Affiliations

  1. Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Meknes, Morocco

    Soukaina Bouamrane, Ayoub Khaldan, Halima Hajji, Reda El-mernissi, Hamid Maghat, Mohammed Aziz Ajana, Abdelouahid Sbai, Mohammed Bouachrine & Tahar Lakhlifi

  2. National Agricultural Research Center, Al-Baqa, 19381, Jordan

    Marwa Alaqarbeh

  3. Department of Chemistry, Faculty of Science, The Hashemite University, Zarqa, Jordan

    Nada Alsakhen

  4. EST Khenifra, Sultan Moulay Sliman University, Benimellal, Morocco

    Mohammed Bouachrine

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  1. Soukaina Bouamrane
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Contributions

SB presented the idea, drafted the project, manipulated the data, analyzed the data, and wrote and revised the manuscript. AK carried out the computations, data processing, and writing. HH and REM contributed to conceptualization and data processing. MA conducted the computations of the molecular dynamics (MD) simulations and reviewed and wrote the paper. NA carried out the computations of the MD simulations. HM analyzed the data, justified the study and reviewed and supervised the project. MAA and AS checked the analytical techniques and supervised the results of this study. MB justified the study and reviewed and supervised the project. TL reviewed, supervised, and administered the project.

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Correspondence to Soukaina Bouamrane.

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Bouamrane, S., Khaldan, A., Hajji, H. et al. In silico identification of 1,2,4-triazoles as potential Candida Albicans inhibitors using 3D-QSAR, molecular docking, molecular dynamics simulations, and ADMET profiling. Mol Divers 27, 2111–2132 (2023). https://doi.org/10.1007/s11030-022-10546-x

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