Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.
Keywords: HIV-associated neurocognitive disorders (HAND); SARS-CoV-2; drug derivatization; hepatitis; human immunodeficiency virus (HIV); infectious diseases; neurodegenerative disorders; prodrugs.