Determination of the inhibition effect of hesperetin and its derivatives on Candida glabrata by molecular docking method


Abstract views: 272 / PDF downloads: 112

Authors

  • Vildan Enisoglu Atalay Uskudar University, Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, 34662, Istanbul, Türkiye https://orcid.org/0000-0002-9830-9158
  • Semse Asar Uskudar University, Institute of Science and Technology, Department of Molecular Biology, 34662, Istanbul, Türkiye https://orcid.org/0009-0004-9172-3366

DOI:

https://doi.org/10.62063/ecb-15

Keywords:

Awp1, Candida glabrata, hesperetin, molecular docking

Abstract

In the study, it was aimed to develop new candidate inhibitor molecules by targeting the AWP1 protein structure of Candida glabrata organism. Hesperetin molecule was taken as a reference and different substituted groups were attached to the determined ends of the molecule to increase the inhibition potential on the protein structure. A total of 100 molecules were designed and after conformer distribution using the Molecular Mechanics/MMFF method for each designed molecule, the area, volume, weight, energy, EHOMO, ELUMO, polarizability, dipole moment, log P values of these molecules were calculated using the Semi Empirical/PM6 method. Molecular docking studies of the optimized molecules were carried out through the Autodock Vina program. After the docking studies, the interactions of the designed molecules with the active site amino acids of the protein structure were analyzed by BIOVIA Discovery Studio Client software in case of possible mutation. As a result of the analysis, five molecules with higher binding energies than other designed molecules and currently used antifungal drugs were recommended.

References

Biovia, D.S.J.S.D.D.S. 2021. Discovery Studio Visualizer v21. 1.0. 20298.

Bongomin, F., Gago, S., Oladele, R.O., & Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. Journal of fungi (Basel, Switzerland), 3(4), 57. https://doi.org/10.3390/jof3040057

Calderone, R.A., & Clancy, C.J. (2012). Candida and candidiasis. American Society for Microbiology Press, 2nd Edition. ASM Press, Washington, DC.

De Groot, P.W., Kraneveld, E.A., Yin, Q.Y., Dekker, H.L., Groß, U., Crielaard, W., de Koster, C.G., Bader, O., Klis, F.M., & Weig, M. (2008). The cell wall of the human pathogen Candida glabrata: differential incorporation of novel adhesin-like wall proteins. Eukaryotic cell, 7(11), 1951–1964. https://doi.org/10.1128/EC.00284-08

Duke, J.A. (1992). Database of biologically active phytochemicals & their activity. CRC Press, pp 1-30. ISBN 9780849336713

Eberhardt, J., Santos-Martins, D., Tillack, A.F., & Forli, S. (2021). AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of chemical information and modeling, 61(8), 3891-3898. https://doi.org/10.1021/acs.jcim.1c00203

Enkler, L., Richer, D., Marchand, A.L., Ferrandon, D., & Jossinet, F. (2016). Genome engineering in the yeast pathogen Candida glabrata using the CRISPR-Cas9 system. Scientific reports, 6, 35766. https://doi.org/10.1038/srep35766

Guinea, J. (2014). Global trends in the distribution of Candida species causing candidemia. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 20 Suppl 6, 5–10. https://doi.org/10.1111/1469-0691.12539

Gupta, P., Gautam, P., Rai, N., & Kumar, N. (2012). An Emerging Hope to Combat Candida albicans: Plant Based Therapeutics. Biotechnology International, 5, 85-114.

Jensen, R., Johansen, H., Søes, L.M., Lemming, L.E., Rosenvinge, F., Nielsen, L., Olesen, B., Kristensen, L., Dzajic, E., & Astvad, K.J.A.A. (2015). Posttreatment antifungal resistance among colonizing Candida isolates in candidemia patients: results from a systematic multicenter study. Antimicrobial agents and chemotherapy, 60(3), 1500-1508. https://doi.org/10.1128/AAC.01763-15

McCarty, T.P., & Pappas, P.G. (2016). Invasive candidiasis. Infectious disease clinics of North America, 30(1), 103-124. https://doi.org/10.1016/j.idc.2015.10.013

Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., & Olson, A.J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of computational chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256

Mota, S., Alves, R., Carneiro, C., Silva, S., Brown, A.J., Istel, F., Kuchler, K., Sampaio, P., Casal, M., Henriques, M., & Paiva, S. (2015). Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate. Frontiers in microbiology, 6, 919. https://doi.org/10.3389/fmicb.2015.00919

Pfaller, M.A., & Diekema, D.J. (2007). Epidemiology of invasive candidiasis: a persistent public health problem. Clinical microbiology reviews, 20(1), 133-163. https://doi.org/10.1128/CMR.00029-06

Seyedmousavi, S., İlkit, M., Durdu, M., Ergin, Ç., Polat, S.H., Melchers, W., & Verweıj, P. (2015). Candida and Candidosis: Updates on Epidemiology, Diagnosis, Treatment, Antifungal Drug Resistance, and Host Genetic Susceptibility. Türk mikrobiyoloji cemiyeti dergisi, 45(1), 1-11. https://doi.org/10.5222/TMCD.2015.001

Tamo, S.P.B. (2020). Candida Infections: Clinical Features, Diagnosis and Treatment. Infectious diseases& clinical microbiology, 2, 91-103. https://doi.org/10.36519/idcm.2020.0006

Timmermans, B., De Las Peñas, A., Castaño, I., & Van Dijck, P. (2018). Adhesins in Candida glabrata. Journal of fungi (Basel, Switzerland), 4(2), 60. https://doi.org/10.3390/jof4020060

Weig, M., Jansch, L., Groß, U., De Koster, C.G., Klis, F.M., & De Groot, P.W.J. (2004). Systematic identification in silico of covalently bound cell wall proteins and analysis of protein–polysaccharide linkages of the human pathogen Candida glabrata. Microbiology (Reading, England), 150(Pt 10), 3129–3144. https://doi.org/10.1099/mic.0.27256-0

Downloads

Published

2024-01-02

How to Cite

Enisoglu Atalay, V., & Asar, S. (2024). Determination of the inhibition effect of hesperetin and its derivatives on Candida glabrata by molecular docking method. The European Chemistry and Biotechnology Journal, (1), 27–38. https://doi.org/10.62063/ecb-15

Issue

Section

Research Articles