A level – Antiviral amino acid ester prodrugs

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New viruses are emerging, requiring new drugs for protection that can work effectively in the body. Broad-spectrum drugs are preferred because they are cost-effective and reduce the risk of resistance. Thiazolides, such as Nitazoxanide and RM5038, are examples of anti-infective agents.
Prodrugs are inactive compounds that become active through chemical changes in the body. Amino acid ester prodrugs (AAEPs) improve drug solubility but are unstable and break down easily. When they break down, they form peptides with strong antiviral activity and better pharmacokinetics, such as reduced clearance and improved solubility.
In this study, prodrugs 5a and 6 are AAEP versions of Nitazoxanide and RM5038, with a bulky group (purple) replacing a part of the chemical structure for better stability. The breakdown product 5a forms active pseudotripeptide 8 with antiviral effects, while tripeptide 20 is more stable but inactive in antiviral essays.

For further information, visit the degree page for amino acid ester prodrugs.

A. V. Stachulski, J.-F. Rossignol, S. Pate, J. Taujanskas, J. A. Iggo, R. Aerts, E. Pascal, S. Piacentini, S. La Frazia, M. G. Santoro, L. van Vooren, L. Sintubin, M. Cooper, K. Swift and P. M. O’Neill, ACS Bio & Med Chem Au, 2023, 3, 327-334.