Open Access Open Access  Restricted Access Subscription or Fee Access

INVESTIGATING PHYTOCHEMICAL INHIBITORS OF PSEUDOMONAS AERUGINOSA'S AHL SYNTHASE LASI: A PATH TOWARD NOVEL THERAPEUTIC AGENTS

Priyanshu KV

Abstract


 Objectives: This study intended to explore the potential of phytochemicals from Allium sativum to inhibit AHL synthase LasI, a critical protein of the Quorum Sensing (QS) pathway in Pseudomonas aeruginosa, with the ultimate objective of developing therapeutic agents for managing P. aeruginosa infections. Methods: The physicochemical properties, toxicity, aggregation ability and binding potential of phytochemicals from Allium sativum to the protein AHL synthase LasI were determined. Physicochemical properties, toxicity and aggregation ability were determined using various in-silico tools. Molecular docking simulations were conducted to study the binding interactions between the selected phytochemicals and AHL Synthase LasI. Results: The investigation revealed that 3 phytochemicals, namely Cyercene 1, Thiamine, and 1-Ethylquinolinium iodide, exhibited promising physicochemical properties, low toxicity, and the ability to prevent aggregation. Molecular docking simulations demonstrated strong binding interactions between these ligands and AHL synthase LasI, suggesting their potential as inhibitors of the QS system in P. aeruginosa. Conclusion: Inhibition of AHL synthase LasI is a crucial step in disrupting the QS pathway of P. aeruginosa. The findings of this study indicate that Cyercene 1, Thiamine, and 1-Ethylquinolinium iodide are promising candidates for the development of therapeutic drugs to target LasI, which could be a viable approach for managing infections. Further research and development of these compounds may lead to effective treatments for P. aeruginosa-related diseases, particularly in healthcare settings where the pathogen often spreads through contaminated water and soil.

 


Keywords


Pseudomonas aeruginosa, Allium sativum, binding affinity, therapeutic agents, ligand docking, in-silico studies.

Full Text:

PDF

References


Urado-Martín, I., Sainz-Mejías, M., & McClean, S. (2021). Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors. International Journal of Molecular Sciences, 22(6), 3128. https://doi.org/10.3390/ijms22063128

Thi, M. T. T., Wibowo, D., & Rehm, B. H. A. (2020). Pseudomonas aeruginosa Biofilms. International journal of molecular sciences, 21(22), 8671. https://doi.org/10.3390/ijms21228671

Benzie, I., & Wachtel-Galor, S. (Eds.). (2011). Herbal Medicine: Biomolecular and Clinical Aspects. (2nd ed.). CRC Press/Taylor & Francis

Mohanraj, K., Karthikeyan, B. S., Vivek-Ananth, R. P., Chand, R. P., Aparna, S. R., Mangalapandi, P., & Samal, A. (2018). IMPPAT: a curated database of Indian medicinal plants, phytochemistry and therapeutics. Scientific reports, 8(1), 1-17

Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., & Bolton, E. E. (2021). PubChem in 2021: new data content and improved web interfaces. Nucleic acids research, 49(D1), D1388–D1395. https://doi.org/10.1093/nar/gkaa971

Burley, S. K., Berman, H. M., Kleywegt, G. J., Markley, J. L., Nakamura, H., & Velankar, S. (2017). Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive. Methods in molecular biology (Clifton, N.J.), 1607, 627–641. https://doi.org/10.1007/978-1-4939-7000-1_26

Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. Chemical biology: methods and protocols, 243-250.

Baroroh, U., Biotek, M., Muscifa, Z. S., Destiarani, W., Rohmatullah, F. G., & Yusuf, M. (2023). Molecular interaction analysis and visualization of protein-ligand docking using Biovia Discovery Studio Visualizer. Indonesian Journal of Computational Biology (IJCB), 2(1), 22-30.

McWilliam, H., Li, W., Uludag, M., Squizzato, S., Park, Y. M., Buso, N., ... & Lopez, R. (2013). Analysis tool web services from the EMBL-EBI. Nucleic acids research, 41(W1), W597-W600

Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic acids research, 46(W1), W257-W263

Yang, Z. Y., Yang, Z. J., Dong, J., Wang, L. L., Zhang, L. X., Ding, J. J., ... & Cao, D. S. (2019). Structural analysis and identification of colloidal aggregators in drug discovery. Journal of chemical information and modeling, 59(9), 3714-3726

de Beer, T. A., Berka, K., Thornton, J. M., & Laskowski, R. A. (2014). PDBsum additions. Nucleic acids research, 42(Database issue), D292–D296. https://doi.org/10.1093/nar/gkt940

Bjarnsholt, T. (2005). Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology, 151(12), 3873–3880. doi:10.1099/mic.0.27955-0




DOI: https://doi.org/10.37591/rrjocb.v12i3.3395

Refbacks

  • There are currently no refbacks.