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Recent developments in phosphorus-containing ester prodrugs and its prospectives
- 1 Wuhan University
- 2 Wuhan University
* Author to whom correspondence should be addressed.
Abstract
Prodrugs has been established as a strategy to improve the medical properties of their parent drugs, and thereby enhance the possibility of these potential drugs to cure the disease but this modified drugs should be cautious as their properties like issue distribution, efficacy and toxicity may change. In the current developed modifying strategies, esterification is among the most common ones, which masks charged hydrophilic groups with ester promoieties so that permeation ability of drugs through the membrane will enhance. Among various esters, phosphorus-containing ester prodrugs are attractive due to close relationship between atom phosphorus and key bioactive compounds including DNA or RNA, phospholipid, proteins. Herein, we will review the developments of these prodrugs, especially phosphate and phosphonate prodrugs, their synthetic methods, pros and cons, application and methods for characterization, with which specific examples or clinical trials will be attached for clearer description Ultimately, we prospect that the phosphorus-containing prodrugs will for certain be further studied and improved and be an indispensable role in medical cares.
Keywords
ester prodrugs, phosphorus
[1]. Diaz, M. E., Pena, R. E., Lobo, M., Schmid, R. A., Binkhathlan, F. H., & Tschinke, M. (2022). Advances in high‐throughput mass spectrometry in drug discovery. EMBO Molecular Medicine, 15(e14850).
[2]. Buckley, V., Thakkar, B., Patel, S. H., & Robins, M. R. A. (2020). High-Throughput Screening: today’s biochemical and cell-based approaches. Drug Discovery Today, 25(10).
[3]. Liu, R., Li, X., & Lam, K. S. (2017). Combinatorial chemistry in drug discovery. Current Opinion in Chemical Biology, 38, 117.
[4]. Kennedy, J. P., Williams, L., Borchardt, T. M., Daniels, R. N., Wiest, D., & Lindsley, C. W. (2008). Application of combinatorial chemistry science on modern drug discovery. Journal of Combinatorial Chemistry, 10, 345.
[5]. Venkatesh, S., & Lipper, R. A. (2004). Role of the development scientist in compound lead selection and optimization. Journal of Pharmaceutical Sciences, 89, 145.
[6]. Rautio, J., Kumpulainen, H., & Heimbach, T. (2008). Prodrugs: design and clinical applications. Nature Reviews Drug Discovery, 7, 255.
[7]. Rodriguez, J. B., & Gallo-Rodriguez, C. (2019). Chem. Med. Chem., 14, 190.
[8]. Fang, S., Liu, Z., & Wang, T. (2023). Recent Advances of the Atherton-Todd Reaction. Chinese Journal of Organic Chemistry, 43, 1069.
[9]. Kourounakis, S., & Pappas, G. (2022). Improvements, variations and biomedical applications of the Michaelis–Arbuzov reaction. International Journal of Molecular Sciences, 23(3395).
[10]. Mao, X., Chen, J., & Yao, Y. (2024). Progress in phosphorylation of natural products. Molecular Biology Reports, 51, 697.
[11]. Mehellou, Y., Singh, H. R., & Balzarini, J. (2018). The ProTide Prodrug Technology: From the Concept to the Clinic. Journal of Medicinal Chemistry, 61, 2211.
[12]. Mehellou, Y., McGuigan, C., Brancale, A., & Balzarini, J. (2007). Design, synthesis, and anti-HIV activity of 2’,3’-didehydro-2’,3’-dideoxyuridine (d4U), 2’,3’-dideoxyuridine (ddU) phosphoramidate ‘ProTide’ derivatives. Bioorganic & Medicinal Chemistry Letters, 17, 3666.
[13]. Ying, H., Yao, J., Wu, F., Zhao, Y., & Ni, F. (2022). A mild and concise synthesis of aryloxy phosphoramidate prodrug of alcohols via transesterification reaction. RSC Advances, 12, 13111.
[14]. Yao, J., Huang, C., Wu, F., Ni, F., & Zhao, Y. (2022). Synthesis of phosphoramidate prodrugs of phenolic natural products and drugs by ester exchange. Synthesis, 54, 3005.
[15]. Chen, F., Huang, G., Yang, Z., & Hou, Y. (2019). Antioxidant activity of Momordica charantia polysaccharide and its derivatives. International Journal of Biological Macromolecules, 138, 673.
[16]. Zhou, S.; Huang, G.Preparation, Structure and activity of polysaccharide phosphate esters. Biomed. Pharmacother. 2021, 144, 112332.
[17]. Hu, H., Li, H., Han, M., Cao, Q., Liang, H., & Yuan, R. (2020). Chemical modification and antioxidant activity of the polysaccharide from Acanthopanax leucorrhizus. *Carbohydrate Research, 487*, 107890.
[18]. Hu, S., Song, L., Pan, H., Hu, Y., & Gong, X. (2012). Thermal properties and combustion behaviors of flame retarded epoxy acrylate with a chitosan based flame retardant containing phosphorus and acrylate structure. Journal of Analytical and Applied Pyrolysis, 97, 109.
[19]. Kim, W., Haws, H., Peterson, P., Whatcott, C. J., Weitman, S., Warner, S. L., et al. (2017). TP‐1287, an oral prodrug of the cyclin‐dependent kinase‐9 inhibitor alvocidib. Cancer Research, 77(19), 5133.
[20]. Mao, X., Chen, J., & Yao, Y. (2024). Progress in phosphorylation of natural products. Molecular Biology Reports, 51(2), 697.
[21]. Patil, S., Lis, L. G., Schumacher, R. J., Norris, B. J., Morgan, M. L., Cuellar, R. A., et al. (2015). Phosphonooxymethyl prodrug of triptolide: synthesis, physicochemical characterization, and efficacy in human colon adenocarcinoma and ovarian cancer xenografts. Journal of Medicinal Chemistry, 58(24), 9334.
[22]. Guo, C., & Huang, B. (2021). Study on preparation and activity of phosphates derivatives of Epimedium flavonoids. Guangdong University of Technology.
[23]. Erion, M. D., van Poelje, P. D., Mackenna, D. A., Colby, T. J., Montag, A. C., & Fujitaki, J. M. (2005). Liver-targeted drug delivery using HepDirect prodrugs. Journal of Pharmacology and Experimental Therapeutics, 312(2), 554.
[24]. Rebecca, E. F., Harrison, S., Ryan, J. M., Danielle, S., & Liu, G.-J. (2024). RSC Med. Chem., 15, 1973.
[25]. Li, J., Wang, L., Han, M., Xiong, Y., & Liao, R. (2019). The role of phosphate-containing medications and low dietary phosphorus-protein ratio in reducing intestinal phosphorus load in patients with chronic kidney disease. Nutrition & Diabetes, 9(1), 14.
[26]. Bharate, S. S., & Vishwakarma, R. A. (2015). Thermodynamic equilibrium solubility measurements in simulated fluids by 96-well plate method in early drug discovery. Bioorganic & Medicinal Chemistry Letters, 25(8), 1561.
[27]. Xia, S., Zhai, Y., Wang, X., Fan, Q., Dong, X., & Chen, M. (2021). Phosphorylation of polysaccharides: a review on the synthesis and bioactivities. International Journal of Biological Macromolecules, 184, 946.
[28]. Ruthes, A. C., Carbonero, E. R., Córdova, M. M., Baggio, C. H., & Santos, A. R. (2013). Lactarius rufus (1→3), (1→6)-β-D-glucans: structure, antinociceptive and anti-inflammatory effects. Carbohydrate Polymers, 94(1), 129.
[29]. Erion, M. D., Reddy, K. R., Boyer, S. H., Matelich, M. C., & Jorge, G.-G. (2004). Journal of the American Chemical Society, 126(15), 5154.
Cite this article
Huang,X.;Fu,J. (2025). Recent developments in phosphorus-containing ester prodrugs and its prospectives. Journal of Food Science, Nutrition and Health,3,49-57.
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