Structure Modification: a Successful Tool for Prodrug Design

Abstract

Prodrug strategy is critical for innovative drug development. Structural modification is the most straightforward and effective method to develop prodrugs. Improving drug defects and optimizing the physical and chemical properties of a drug, such as lipophilicity and water solubility, changing the way of administration can be achieved through specific structural modification. Designing prodrugs by linking microenvironment-responsive groups to the prototype drugs is of great help in enhancing drug targeting. In the meantime, making connections between prodrugs and suitable drug delivery systems could realize drug loading increases, greater stability, bioavailability and drug release control. In this paper, lipidic, water-soluble, pH-responsive, redox-sensitive and enzyme-activatable prodrugs are reviewed on the basis of structural modification.

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

“…Given the vulnerability of drug structure, the conventional structural modification strategies of drugs were introduced in the review ( Cheng et al, 2023 ). Here, we mainly summarized the protection strategies of nanotechnology for drug stability, including the encapsulation of drugs by nanomaterials, improving surface characteristics, and modifying nanomaterials.…”

Structural optimization of icaritin for advanced cancer: novel carbamates via oral administration

“…The carbamate strategy, which involves chemically modifying the structure of the drug itself to improve the bioavailability of the drug, is routinely used to improve the phase II metabolic stability of some flavonoids, such as resveratrol and baicalein. 31–34 Due to the effect of the electron-donating groups on the carbamate bond and the esterase inhibitory activity of the carbamates, carbamates have good stability and can avoid being broken down before entering the body. 35 Besides, structure–activity relationship analysis revealed that mono-substitution at the 3-OH group of ICT could improve the cytotoxicity of cancer cells.…”